The blood cell phosphatidylinositol glycan class A (PIG-A) gene mutation assay has been extensively researched in rodents for in vivo mutagenicity testing and is now being investigated in humans. The PIG-A gene is involved in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis. A single mutation in this X-linked gene leads to loss of membrane bound GPI-anchors, which can be enumerated using flow cytometry. With many studies published to date measuring this mutation in erythrocytes, there is remarkable consistency across research groups. Moreover, with the low background level of mutant erythrocytes in healthy subjects (2.9 - 5.56 x 10-6 mutants), induction of mutation post genotoxic exposure can be detected. Cigarette smoking, radiotherapy and occupational exposures including lead, have been shown to increase mutant levels. Identification of harmful agents can allow us to recommend new exposure limits, minimising individual risk. Conversely, protective agents such as aspirin and healthy diets could mitigate these effects, reducing baseline somatic mutation levels and such behaviours can be encouraged. This mutational monitoring approach may also provide information on individuals at higher risk of cancer development. Patients with inflammatory bowel disease, oesophageal adenocarcinoma and pancreatic cancer have elevated numbers of PIG-A mutant erythrocytes compared to age-matched controls. With further technological progress including protocol standardisation and the development of cryopreservation methods to improve GPI-anchor stability, this assay can be widely employed in rural and low-income countries. Here we review the current literature on PIG-A mutation in human subjects and discuss the potential role of this assay in human biomonitoring and disease.
Monitoring of sweat pH play important roles in physiological health, nutritional balance, psychological stress, and sports performance. The combination of functional MOFs with phosphorescent material to acquire the real-time physiological information, as well as the ap-plication of dual mode anti-counterfeiting, have seldom been reported. Herein, we reported MOF and phosphorescent dyes based mul-tifunctional gel films with H+ response and the related mechanism was studied in detail. Upon induction of H+, the composite gel film ex-hibited decreased fluorescent signal but enhanced room temperature phosphorescence (RTP), which could be utilized for sweat pH sensing through a dual-mode. Moreover, multifunctional gel films exhibited a potential application in information encryption and an-ti-counterfeiting by designing of stimulus responsive multiple patterns. This research opens a new avenue for portable and non-invasive sweat pH monitoring method, provides opportunities for effective anti-counterfeiting, also offers new insights stimulus-responsive mul-tifunctional materials and their potential applications.
Photoresponsive supramolecular materials have been fabricated by controlling the density of reversible cross-links or the distribution of movable cross-links. This study prepared photoresponsive polyurethane (CD-Azo-PU) based on controlling the crystallization of the hard segments in polyurethane (PU) by complexation between azobenzene (Azo) and cyclodextrins (CDs). CD-Azo-PU incorporated polyurethane as the main chain and a 1:2 inclusion complex between Azo and γCD as a movable crosslink point. Upon ultraviolet light (UV, λ = 365 nm) irradiation, the photoresponsiveness of CD-Azo-PU bent toward the light source (defined as positive), while that of the linear Azo polyurethane (Azo-LPU) without TAcγCD-diOH as a movable crosslinker bent in the direction opposite the light source. The bending rates were determined to be 0.058°/s for CD-Azo-PU and 0.027°/s for Azo-LPU, indicating that the bending rate for CD-Azo-PU was faster than that for Azo-LPU. By incorporating movable cross-links into CD-Azo-PU, we successfully achieved specific photoresponsive actuation with an enhanced rate.
Background and Purpose: P2X4 receptors (P2X4R) are ligand gated cation channels that are activated by extracellular adenosine 5′-triphosphate (ATP) released by neurons and glia. The receptors are widely expressed in the brain and have fractional calcium currents comparable to NMDA receptors. Although P2X4Rs were described to modulate synaptic transmission and plasticity, their involvement in shaping neuronal network activity remains to be elucidated. Exp. Approach: We investigated the effects of P2X receptors on network and synaptic level using local field potential electrophysiology, whole cell patch clamp recordings and calcium imaging in fast spiking parvalbumin positive interneurons (PVINs) in rat and mice hippocampal slices. The stable ATP analogue ATPγS, selective antagonists and P2X4R knockout mice were used. Key results: The P2XR agonist ATPγS reversibly decreased the power of gamma oscillations. This inhibition could be antagonized by the selective P2X4R antagonist PSB-12062 and was not observed in P2X4-/- mice. The phasic excitatory inputs of CA3 PVINs were one of the main regulators of the gamma power. Associational fibre compound excitatory postsynaptic currents (cEPSCs) in CA3 PVINs were inhibited by P2X4R activation. This effect was reversible, dependent on intracellular calcium and dynamin-dependent internalization of AMPA receptors. Conclusions and Implications: The results indicate that P2X4Rs are an important source of dendritic calcium in CA3 PVINs, thereby regulating excitatory synaptic inputs onto the cells and the state of gamma oscillations in the hippocampus. P2X4Rs represent an effective target to modulate hippocampal network activity in pathophysiological conditions such as Alzheimer’s disease and schizophrenia.
The recent uptick in the approval of ex vivo cell therapies highlight the relevance of Lentivirus (LV) as an enabling viral vector of modern medicine. As labile biologics, however, LVs pose critical challenges to industrial biomanufacturing. In particular, LV purification – currently reliant on filtration and anion-exchange or size-exclusion chromatography – suffers from long process times and low yield of transducing particles, which translate in high waiting time and cost to patients. Seeking to improve LV downstream processing, this study introduces peptides targeting the enveloped protein Vesicular stomatitis virus G (VSV-G) to serve as affinity ligands for the chromatographic purification of LV particles. An ensemble of candidate ligands was initially discovered by implementing a dual-fluorescence screening technology and a targeted in silico approach designed to identify sequences with high selectivity and tunable affinity. The selected peptides were conjugated on Poros resin and their LV binding-and-release performance was optimized by adjusting the flow rate, composition, and pH of the chromatographic buffers. Ligands GKEAAFAA and SRAFVGDADRD were selected for their high product yield (50-60% of viral genomes; 40-50% of HT1080 cell-transducing particles) upon elution in PIPES buffer with 0.65 M NaCl at pH 7.4. The peptide-based adsorbents also presented remarkable values of binding capacity (up to 3·10 9 TU per mL of resin at the residence time of 1 min) and clearance of host cell proteins (up to 220-fold reduction of HEK293 HCPs). Additionally, GKEAAFAA demonstrated high resistance to caustic cleaning-in-place (0.5 M NaOH, 30 min) with no observable loss in product yield and quality.
We present a complete portable pipeline for sequencing and analysis of environmental metagenomes in less than a day. This unprecedented development was possible due to the conjunction of state-of-the art experimental and computational advances: a portable laboratory suitable for DNA extraction and sequencing with nanopore technology.The powerful metagenomic analysis pipeline SqueezeMeta, capable to provide a complete analysis in a few hours and using scarce computational resources. Finally, tools for the automatic inspection of the results via a graphical user interface, that can be coupled to a web server to allow remote visualization of data (SQMtools and SQMxplore). We tested the feasibility of our approach in the sequencing of the microbiota associated to volcanic rocks in La Palma, Canary Islands. Also, we did a two-day sampling campaign of marine waters in which the results obtained the first day guided the experimental design of the second day. We demonstrate that it is possible to generate metagenomic information in less than one day, making it feasible to obtain taxonomic and functional profiles fast and efficiently, even in field conditions. This capacity can be used in the further to perform real-time functional and taxonomic profiling of microbial communities in remote areas
Electrochemical synthesis of green oxidants O3 and H2O2 is valuable for applications, but challenges persist in enhancing the O3 and H2O2 generation activity and combined application. Herein, we modulate the surface Ni active sites and oxygen vacancy defects content in Ni-Sb-SnO2 electrocatalysts to enhance selectivity for electrochemical ozone generation (EOP) and two-electron electrochemical oxygen reduction reactions (2e⁻ ORR). The Ni active sites and oxygen vacancy defects enriched electrocatalysts resulting in an ozone faradaic efficiency of 48.1%, while non-enriched electrocatalyst obtained 90% selectivity for H2O2. Theoretical calculations revealed that Ni-Sb-SnO2 efficiently captures O2 with defective Ovac2 stabilize intermediates, facilitating O3 and H2O2 synthesis. Moreover, concerted EOP and 2e⁻ ORR enable concurrent generation of O3 and H2O2 for efficient synergistic degradation of organic pollutants, while attenuating the energy demands of the electrolyzer. This study provides an appealing strategy for the simultaneous production of O3 and H2O2 with applications in wastewater treatment.
The use of intracytoplasmic sperm injection (ICSI) for the production of equine embryos has significantly increased over the past decade, leading to the creation of labs specific for ICSI and related in vitro fertilization techniques. However, the commitment, resources and skills necessary for developing a viable IVF lab can be underestimated or under-appreciated. The purpose of this paper is to share the difficulties our clinic encountered when developing an IVF lab.
Photothermal devices and thermoelectric cells hold great promise for energy generation but integration of the two remains a considerable challenge in real-life power supply for sensors. Here, a novel photo-thermo-electric hydrogel (PTEH-Interlocking) was constructed by synthesis of a photothermal layer on a thermoelectric hydrogel with the redox pair Fe(CN)63−/Fe(CN)64−. The smart design of using oxidation of pyrogallic acid by Fe(CN)63− to construct the photothermal layer for photo-to-heat conversion protected the redox couple of the thermogalvanic ion pair from ultraviolet damage, as well as triggered the formation of an interlocking structure at the interface of the photothermal layer and the thermoelectric hydrogel. The as-prepared PTEH-Interlocking have shown a high Seebeck coefficient and rapid heat transfer, boosting the photo-thermo-electric conversion. As a demonstration of a practical application, the PTEH-Interlocking cells is successfully used as the energy supply for a mechanical sensor.
Title: Castleman disease presenting as a longstanding axillary and chest wall mass: A case reportWenqing Zhou1*, Xing Liu2*, Aiming Qiu3*, Teng Ni4, Tiangeng Dong5, Lei Ding6Wenqing Zhou, Xing Liu and Aiming Qiu contributed equally to this workCorrespondence should be addressed to Tiangeng Dong; [email protected] and Lei Ding; [email protected]: Castleman disease is a rare lymphoproliferative disorder that can present with various clinical features. We present a case of a 30-year-old female with a progressively enlarging mass in the left axilla and chest wall for ten years. After diagnostic workup, including ultrasonography, MRI, and core needle biopsy, the patient underwent surgical excision of the mass. The diagnosis of Castleman disease was confirmed through pathological and immunohistochemical examinations. The patient recovered well postoperatively with a good prognosis.Keyword: Castleman disease, axillary, chest wallIntroduction: Castleman disease, first described in 1956 by Dr. Benjamin Castleman, is a rare lymphoproliferative disorder. This disease can affect any lymphoid tissue in the body and present with localized or systemic symptoms. The diagnosis is based on pathological examination, and the disease has a varied clinical course and response to treatment.Case report: The patient was a 30-year-old female with a ten-year history of a progressively enlarging mass in the left axilla and chest wall (Figure 1). The mass was initially small and asymptomatic but had gradually increased in size over the years. The patient had no significant medical history or family history of lymphoproliferative disorders.Diagnostic workup, including ultrasonography(Figure 2) and MRI[Figure 3A,3B], revealed a well-circumscribed, heterogeneously enhancing mass measuring 10 x 6 x 3 cm . A core needle biopsy was performed, and pathological and immunohistochemical examinations revealed clonal lymphoid proliferation within fibrotic stroma (Figure 4A,4B). The histopathological features were consistent with the hyaline vascular variant of Castleman disease .After appropriate preoperative preparation, the patient underwent surgical excision of the mass. Intraoperative findings revealed a well-encapsulated mass that was adherent to the chest wall muscles. The mass was completely excised with negative margins. Postoperative recovery was uneventful, and the patient was discharged on postoperative day 5.Histopathological examination of the excised mass confirmed the diagnosis of Castleman disease. The immunohistochemical profile was consistent with the hyaline vascular variant, which is characterized by clonal proliferation of B-cells with follicular dendritic cell expansion.Discussion: Castleman disease is a rare lymphoproliferative disorder that can present with varied clinical features. The disease has two major histological subtypes: hyaline vascular and plasma cell. The more common hyaline vascular subtype presents with localized lymphadenopathy, while the less common plasma cell subtype is associated with systemic symptoms and multiorgan involvement.Diagnosis of Castleman disease requires a combination of clinical, radiological, and pathological findings. Treatment options include surgery, radiation therapy, and chemotherapy, depending on the subtype, stage, and extent of the disease. The localized hyaline vascular subtype generally has a good prognosis, while the systemic plasma cell subtype has a more variable clinical course.Conclusion: Castleman disease should be considered as a differential diagnosis for longstanding masses in lymphoid tissue. Appropriate diagnostic workup, including imaging and pathological examinations, is crucial for accurate diagnosis and optimal management. Surgical excision can offer a curative treatment with a good prognosis for the localized hyaline vascular subtype .AcknowledgmentsThis work was supported by grants from the Science and Education Foundation of Wujiang District (wwk202019).References: Oksenhendler E. The Spectrum of Castleman’s Disease and its Treatment. Hematology Am Soc Hematol Educ Program. 2016;2016(1):327-334. Chan KL, Tong J, Loong F, et al. Castleman’s disease: a report of 18 cases from a single institution. J Clin Oncol. 1998;16(5):1988-1995. Soumerai JD, Sohani AR, Abramson JS. Diagnosis and management of Castleman disease. Cancer Control. 2014;21(4):266-278. Dispenzieri A. Castleman disease. Hematology Am Soc Hematol Educ Program. 2018;2018(1):324-329. doi:10.1182/asheducation-2018.1.324 Liu AY, Nabel CS, Finkelman BS, et al. Idiopathic multicentric Castleman’s disease: a systematic literature review. Lancet Haematol. 2016;3(4):e163-e175. doi:10.1016/S2352-3026(16)00015-X Talat N, Belgaumkar AP, Schulte KM. Surgery in Castleman’s disease: a systematic review of 404 published cases. Ann Surg. 2012;255(4):677-684. doi:10.1097/SLA.0b013e31824a57e9 van Rhee F, Stone K, Szmania S, Barlogie B, Singh Z. Castleman disease in the 21st century: an update on diagnosis, assessment, and therapy. Clin Adv Hematol Oncol. 2010;8(7):486-498
Prior studies found hand preference trajectories predict preschool language outcomes. However, this approach has been limited to examining bimanual manipulation in toddlers. It is not known whether hand preference during infancy for acquiring objects (i.e., reach-to-grasp) similarly predicts childhood language ability. The current study explored this motor-language developmental cascade in 90 children. Hand preference for acquiring objects was assessed monthly from 6 to 14 months and language skill was assessed at 5 years. Latent class growth analysis identified three infant hand preference classes: left, early right, and late right. Infant hand preference classes predicted 5-year language skills. Children in the left and early right classes, who were categorized as having a consistent hand preference, had higher expressive and receptive language scores relative to children in the inconsistent late right class. Consistent classes did not differ from each other on language outcomes. Infant hand preference patterns explained more variance for expressive and receptive language relative to previously reported toddler hand preference patterns, above and beyond socioeconomic status (SES). Results suggest that hand preference, measured at different time points across development using a trajectory approach, is reliably linked to later language.
IntroductionMetastasis in the testes is a relatively rare occurrence, accounting for only 0.02% to 2.5% of all testicular tumors and is more common in older individuals. Identifying the primary site of tumors that resemble those found in both the gastrointestinal tract (GIT) and testis can be challenging. This is where immunohistochemistry plays a crucial role in making an accurate diagnosis, leading to proper treatment.While primary malignancies in the small intestine are uncommon, accounting for only about 2.3% of all malignancies in the digestive system and 0.42% of all malignancies, it is essential to recognize the rare subtypes, such as signet-ring cell carcinoma (SRCC). SRCC is typically found in the stomach, but it can also occur in other organs such as the pancreas, breasts, bladder, ovaries, esophagus, lungs, and large intestine.This report highlights an unusual case of a 44-year-old male patient with signet-ring cell mucinous adenocarcinoma metastasis of unknown source in the right testis, possibly originating from the small intestine.case presentation :A 44-year-old male presented with right testicular swelling, heaviness, and weight loss for the past 3 months. He is a heavy smoker and non-alcoholic with no past medical, surgical, or family history. The physical examination was normal except for the painful testicular mass. Echography of the testis showed a solid mass measuring 10.5x8x6 cm in the right testicle with irregular borders and increased vascularity. A Computerized Tomography (CT) scan with contrast showed multiple metastases within the chest lymph nodes, ribs, liver, pancreas, adrenal glands, periaortic lymph nodes, axillary lymph nodes, and groin lymph nodes. Bone scintigraphy demonstrated abnormal accumulation of the radiotracer in the 2nd and 7th ribs, the head of the left humerus, and throughout the right femur. The previous tests assumed a primary testicular cancer with metastasis, although alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (HCG) were normal. The team excised the right painful testicle and sent it for pathological studies.Surprisingly, the pathology report of the right testicle came with a final diagnosis of testicular signet-ring cell carcinoma metastasis (Figure 1) with positive CK7, CK20, and CDX2 immunostains (Figure 2), which suggests a primary origin from either the stomach or small intestine. The upper and lower endoscopies with biopsies from the stomach and colons were normal. In line with the pathology report, the team suspected that the tumor was most likely from the small intestine. However, we could not confirm our suspicion due to the lack of equipment that can visualize the small intestine. Therefore, the primary origin of the tumor remains unknown.SRCC is a rare and aggressive type of cancer that can explain the presence of multiple metastatic lesions in this patient. So, no further evaluation was performed to look for other metastatic sites due to the critical condition of the patient at the time of presentation. And the team suggested FOLFOX chemotherapy treatment protocol, after ruling out the gastric origin and suspecting intestinal origin. Follow up is not yet reported.Figure 1: Proliferation of signet ring cells with the displacement of the nucleus to the side by intracellular mucin. With accumulation of extracellular mucin.Figure 2 A, B: CK20 Positive immunostain. C, D: CK7 Positive immunostain. E, F: CDX20 Positive Immunostain