Critical Suitability Evaluation of Caco-2 Cells for Gut-on-a-Chip.

Currently, culturing Caco-2 cells in a Gut-on-a-chip (GOC) is well-accepted for developing intestinal disease models and drug screening. However, Caco-2 cells were found to overexpress surface proteins (e.g., P-gp) compared with the normal intestinal epithelial cells in vivo. To critically evaluate the challenge and suitability of Caco-2 cells, a GOC integrated with a carcinoembryonic antigen (CEA) biosensor was developed. This three-electrode system electrochemical sensor detects CEA by antigen-antibody specific binding, and it exhibits high selectivity, excellent stability, and good reproducibility. Under dynamic culturing in the GOC, Caco-2 cells exhibited an intestinal villus-like structure and maintained tissue barrier integrity. Meanwhile, CEA was discovered to be secreted from 0 to 0.22 ng/mL during the 10-day culturing of Caco-2 cells. Especially, CEA secretion increased significantly with the differentiation of Caco-2 cells after 6 days of culturing. The sustained high-level CEA secretion may induce cells to avoid apoptotic stimuli, which faithfully reflects the efficacy of a new drug and the mechanism of intestinal disease. Different kinds of cell types (e.g., intestinal primary cells, stem cell-induced differentiation) in the GOC should be attempted for drug screening in the future.

LncRNA ACVR2B-as1 interacts with ALDOA to regulate the self-renewal and apoptosis of human spermatogonial stem cells by controlling glycolysis activity.

Human spermatogonial stem cells (SSCs) have significant applications in reproductive medicine and regenerative medicine because of their great plasticity. Nevertheless, it remains unknown about the functions and mechanisms of long non-coding RNA (LncRNA) in regulating the fate determinations of human SSCs. Here we have demonstrated that LncRNA ACVR2B-as1 (activin A receptor type 2B antisense RNA 1) controls the self-renewal and apoptosis of human SSCs by interaction with ALDOA via glycolysis activity. LncRNA ACVR2B-as1 is highly expressed in human SSCs. LncRNA ACVR2B-as1 silencing suppresses the proliferation and DNA synthesis and enhances the apoptosis of human SSCs. Mechanistically, our ChIRP-MS and RIP assays revealed that ACVR2B-as1 interacted with ALDOA in human SSCs. High expression of ACVR2B-as1 enhanced the proliferation, DNA synthesis, and glycolysis of human SSCs but inhibited their apoptosis through up-regulation of ALDOA. Importantly, overexpression of ALDOA counteracted the effect of ACVR2B-as1 knockdown on the aforementioned biological processes. Collectively, these results indicate that ACVR2B-as1 interacts with ALDOA to control the self-renewal and apoptosis of human SSCs by enhancing glycolysis activity. This study is of great significance because it sheds a novel insight into molecular mechanisms underlying the fate decisions of human SSCs and it may offer innovative approaches to address the etiology of male infertility.

"A diamond-shaped" penoplasty technique with or without concurrent suprapubic liposuction for adult-acquired buried penis: clinical outcomes and patient satisfaction rates.

Various techniques have been described for reconstructing the skin of the penile shaft; however, no universally accepted standard exists for correcting buried penis in adults. We aimed to describe a new technique for correcting an adult-acquired buried penis through a diamond-shaped incision at the penopubic junction. We retrospectively analyzed data from patients treated with our technique between March 2019 and June 2023 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Forty-two adult males with buried penises, with a mean (±standard deviation [s.d.]) age of 26.6 (±6.6) years, underwent surgery. All patients were obese, with an average (±s.d.) body mass index of 35.56 (±3.23) kg m-2. In addition to phalloplasty, 32 patients concurrently underwent circumcision, and 28 underwent suprapubic liposuction. The mean (±s.d.) duration of the operation was 98.02 (±13.28) min. The mean (±s.d.) duration of follow-up was 6.71 (±3.43) months. The length in the flaccid unstretched state postoperatively was significantly greater than that preoperatively (mean ± s.d: 5.55±1.19 cm vs 1.94±0.59 cm, P < 0.01). Only minor complications, such as wound disruption (7.1%) and infection (4.8%), were observed. The mean (±s.d.) score of patient satisfaction was 4.02 (±0.84) on a scale of 5. This technique provides excellent cosmetic and functional outcomes with a minimal risk of complications. However, additional clinical studies are needed to evaluate the long-term effects of this procedure.

The Elabela-APJ axis attenuates sepsis-induced myocardial dysfunction by reducing pyroptosis by balancing the formation and degradation of autophagosomes.

BACKGROUND: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD. MATERIALS AND METHODS: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 µM Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins. RESULTS: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis. CONCLUSION: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow.

Close-packed nitronyl nitroxide radicals by Au-S self-assembly: strong ferromagnetic coupling.

The study of the magnetism of tightly arranged nitronyl nitroxide (NN) radicals via Au-S self-assembly is interesting. In this study, a series of radicals (S-NN, D-NN, BS-NN, BD-NN) along with two types of nanomaterials (S-NPs, D-NPs) were synthesized. NN was chosen for the magnetic units. Their structures have been successfully synthesized and analyzed. The spin magnetic properties were characterized by electron paramagnetic resonance (EPR) and superconducting quantum interference device (SQUID) measurement. The analysis revealed that the self-assembled NN formed via Au-S bonds exhibits high packing density. Furthermore, it was gratifying to observe that the AuNPs exhibit ferromagnetism after the surface modification by NN. This results in strong ferromagnetic exchange interactions of S-NPs and D-NPs : J S-NPs = +279.715 K and J D-NPs = +254.913 K, respectively.

C-reactive protein and neutrophil-to-lymphocyte ratio as key inflammatory indicators in the diagnosis of cervical necrotizing fasciitis.

BACKGROUND: Cervical necrotizing fasciitis (CNF) is a life-threatening bacterial infection with a diagnostic challenge. Currently, there is insufficient evidence on the diagnostic accuracy of inflammatory indicators in CNF. OBJECTIVE: This study aims to identify key inflammatory indicators and assess their diagnostic accuracy for CNF. METHODS: A diagnostic case-control study was conducted at a tertiary healthcare facility from January 2020 to December 2023. Laboratory data from patients with CNF and non-CNF at admission were evaluated. Key inflammatory indicators were identified through consistent outcomes from multivariable logistic regression and receiver operating characteristic curves analyses. The diagnostic accuracy of these indicators, with the results of combined tests, were calculated. RESULTS: CNF was confirmed in 21 of the 67 patients investigated. C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) were identified as key inflammatory indicators, with sensitivities of 0.905 and 0.810, and specificities of 0.870 and 0.913, respectively, at CRP threshold of 165.0 mg/L and NLR of 15.8. Combining CRP and NLR in parallel and serial tests increased sensitivity to 0.952 and specificity to 1.0, respectively. CONCLUSIONS AND SIGNIFICANCE: CRP and NLR have been verified as key inflammatory indicators with satisfactory diagnostic abilities for CNF diagnosis, providing a strong foundation for future studies.

Characteristics, clinical significance, and cancer immune interactions of lipid metabolism in prostate cancer.

Background: The relationship between lipid metabolism, immune response, and immunotherapy in prostate cancer (PCa) is closely intertwined, and targeted intervention in lipid metabolism may facilitate the success of anticancer immunotherapy. This research attempted to explore effective immunotherapy for PCa. Methods: We obtained RNA sequencing (RNA-seq) data for PCa patients from the UCSC Xena platform. Data analysis of differentially expressed genes (DEGs) was performed using package limma in R. Then, DEGs were subjected to enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The Human Protein Atlas (HPA) database was conducted to validate the protein expression of the up-regulated lipid metabolism related genes (LMRGs) between PCa tissues and normal prostate tissues. And then we identified critical transcription factors (TFs), LMRGs and miRNA by constructing a regulatory network of TF-gene-miRNA. Furthermore, we determined the high and low groups based on the score of lipid metabolism enrichment. The hallmark gene sets were derived from gene expression profiles using the gene set variation analysis (GSVA) R package. Finally, we conducted immune infiltration analysis and drug sensitivity analysis. Results: Immune response and lipid metabolism have undergone significant changes in PCa and paracancerous tissues compared to normal tissues. A total of 21 LMRGs were differentially up-regulated in PCa. The TF-gene-miRNA network showed that PLA2G7, TWIST1, and TRIB3 may be the key genes that elevated lipid metabolism in PCa. The high group had more infiltration of B cell memory, macrophage M0, macrophage M1, and myeloid dendritic cell resting, and the low group had more infiltration of B cell plasma, monocyte, myeloid dendritic cell activated, and mast cell resting. The majority of checkpoint genes exhibited high expression levels in the low group. Lipid metabolism was remarkedly correlated with drug sensitivity. Conclusions: The analysis of lipid metabolism and related genes has revealed a complex regulatory mechanism that has a significant influence on immune response, immunotherapy, and medication guidance for patients with PCa. Keywords: Prostate cancer (PCa); lipid metabolism; cancer immune; RNA sequencing (RNA-seq).

Synergistically activating nucleophile strategy enabled organocatalytic asymmetric P-addition of cyclic imines.

Herein, we present an attractive organocatalytic asymmetric addition of P-nucleophiles to five-membered cyclic N-sulfonyl imines facilitated by phosphonium salt catalysis, enabling the highly enantioselective synthesis of tri- and tetra-substituted cyclic phosphorus-containing benzosultams. With this protocol, various cyclic α-aminophosphonates were efficiently synthesized with high yields and exceptional enantioselectivities (up to >99% ee) under mild reaction conditions. The utility and practicality of this method were demonstrated through gram-scale reactions and straightforward elaborations. Notably, the success of this approach relies on the deliberate selection of a synergistic organocatalytic system, which helps circumvent foreseeable side effects while handling secondary phosphine oxides (SPOs). Systematic mechanistic studies, incorporating experiments and DFT calculations, have revealed the critical importance of judiciously selecting bifunctional phosphonium salt catalysts for effectively activating P-nucleophiles while stereoselectively controlling the P-attack process.

CXCR4 promotes migration, invasion, and epithelial-mesenchymal transition of papillary thyroid carcinoma by activating STAT3 signaling pathway.

AIMS: Papillary thyroid cancer (PTC) is a serious threat to human health worldwide, while metastasis in the early phase limits therapeutic success and leads to poor survival outcomes. The CXC chemokine receptor type 4 (CXCR4) plays an important role in many cellular movements such as transcriptional modulation, cell skeleton rearrangement, and cell migration, and the change in CXCR4 levels are crucial in various diseases including cancer. In this study, we explored the role of CXCR4 in the migration and invasion of PTC and investigated the potential mechanisms underlying its effects. SUBJECTS AND METHODS: We analyzed the expression levels of CXCR4 in PTC tissues and cell lines. Would healing migration, Transwell invasion assay in vitro, and tail-vein lung metastasis assay In vivo were performed to evaluated the migration and invasion abilities of PTC cells with stable CXCR4 knockdown or overexpression. Signal transducers and activators of transcription (STAT3) signaling pathway-related protein expressions were examined by Western blotting assays. RESULTS: The results showed that CXCR4 was highly expressed in PTC cell lines and PTC tissues. CXCR4 knockdown in PTC cells dampened the migration, invasion, and epithelial-mesenchymal transition (EMT), whereas CXCR4 overexpression enhanced these properties. In vivo, we also found that CXCR4 promoted the metastasis of PTC. Mechanistic studies showed that CXCR4 played these vital roles through the STAT3 signaling pathway. Furthermore, PTC patients with high CXCR4 or p-STAT3 expression correlated with aggressive clinical characteristics such as extrathyroidal extension (ETE), and lymph node metastasis (LNM). CONCLUSIONS: We provided evidence that CXCR4 might activate the STAT3 signaling pathway and further promote PTC development. Thus, CXCR4 might be a novel therapeutic target for PTC.

Synaptic Transistors Using Scalable Graphene Nanoribbons.

Graphene has demonstrated potential for use in neuromorphic electronics due to its superior electrical properties. However, these devices are all based on graphene sheets without patterning, restricting its applications. Here, we demonstrate a graphene nanoribbon synaptic transistor (GNST), with the graphene nanoribbon (GNR) channels fabricated using an electro-hydrodynamically printed nanowire array as lithographic masks for scalable fabrication. The GNST shows tunable synaptic plasticity by spike duration, frequency, and number. Moreover, the device is energy-efficient and ambipolar and shows a regulated response by nanoribbon width. The characteristics of GNSTs are applicable to pattern recognition, showing an accuracy of 84.5%. The device is applicable to Pavlov's classical conditioning. This study reports the first synaptic transistor based on GNRs, providing new insights into future neuromorphic electronics.

Thermally and Mechanically Stable Perovskite Artificial Synapse as Tuned by Phase Engineering for Efferent Neuromuscular Control.

The doping of perovskites with mixed cations and mixed halides is an effective strategy to optimize phase stability. In this study, we introduce a cubic black phase perovskite CsyFA(1-y)Pb(BrxI(1-x))3 artificial synapse, using phase engineering by adjusting the cesium-bromide content. Low-bromine mixed perovskites are suitable to improve the electric pulse excitation sensitivity and stability of the device. Specifically, the low-bromine and low-cesium mixed perovskite (x = 0.15, y = 0.22) annealed at 373 K allows the device to maintain logic response even after 1000 mechanical flex/flat cycles. The device also shows good thermal stability up to temperatures of 333 K. We have demonstrated reflex-arc behavior with MCMHP synaptic units, capable of making sensory warnings at high frequency. This compositionally engineered, dual-mixed perovskite synaptic device provides significant potential for perceptual soft neurorobotic systems and prostheses.

Periphery Biomarkers Predicting Conversion of Type 2 Diabetes to Pre-Alzheimer-Like Cognitive Decline: A Multicenter Follow-Up Study.

Background: The prevalence of Alzheimer's disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD. Objective: To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline. Methods: A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-ß level, platelet GSK-3ß activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure. Results: Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3ß activity, and higher plasma Aß42/Aß40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3ß activity was negatively correlated with brain structures. Conclusions: Elevated platelet GSK-3ß activity and plasma Aß42/Aß40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.

Retinal structural thicknesses reflect clinically relevant microstructural white matter abnormalities in neuromyelitis optica spectrum disorders.

BACKGROUND: Thinning of retinal thickness seen on optical coherence tomography (OCT) is frequent in patients with neuromyelitis optica spectrum disorder (NMOSD). We explored the association between OCT metrics, MRI measurements and clinical outcomes in NMOSD. METHODS: 44 NMOSD and 60 controls underwent OCT and MR imaging. Mean peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) thicknesses were measured. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was used to measure the white matter microstructural integrity. In NMOSD patients, Expanded Disability Status Scale (EDSS) was used to quantify disability. Visual acuity (VA) was also performed for all participants. RESULTS: pRNFL thickness was positively associated with mean diffusivity in left posterior thalamic radiation (pp = 0.010) and axial kurtosis in inferior cerebellar peduncle (p = 0.023). Similarly, GCC thickness in NMOSD patients was positively associated with fractional anisotropy in right superior longitudinal fascicules (p = 0. 041) and axial kurtosis of left cerebellar peduncle (p = 0.011). CONCLUSIONS: In NMOSD, pRNFL and GCC reflect integrity of clinically relevant white matter structures underlying the value of OCT metrics as markers of neuronaxonal loss and disability.

Novel anti-inflammatory peptide alleviates liver ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) remains inevitable in liver surgeries, macrophages play a critical role in the development of IRI, but little is known about the macrophages regulate pathogenesis of IRI. Based on target-guided screening, we identified a small 3 kDa peptide (SjDX5-271) from various schistosome egg-derived peptides that induced M2 macrophage polarization. SjDX5-271 treatment protected the mice against liver IRI through promoting M2 macrophage polarization, the protective effect was abrogated when the macrophages were depleted. Transcriptomic sequencing showed that the TLR signaling pathway was significantly inhibited in macrophages derived from the SjDX5-271 treatment group. We further identified that SjDX5-271 promotes M2 macrophage polarization by inhibiting the TLR4/MyD88/NF-κB signaling pathway and further alleviates hepatic inflammation in liver IRI. Collectively, SjDX5-271 exhibits promising therapeutic effects in IRI and represents a novel therapeutic approach for IRI, even in immune-related diseases. This study revealed the development of a new biologic from the parasite and enhanced our understanding of host-parasite interplay, providing a blueprint for future therapies for immune-related diseases.

SENP1-Mediated deSUMOylation Regulates the Tumor Remodeling of Glioma Stem Cells Under Hypoxic Stress.

Objectives: This study aimed to investigate the effect of specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1)-mediated deSUMOylation on the malignant behavior of glioma stem cells (GSCs) under hypoxia conditions and evaluate the clinical value of prevention in glioma patients. Introductions: Under hypoxic conditions, upregulated hypoxia-inducible factor 1α (HIF1α) expression in GSCs activates Wnt/ß-catenin signaling pathways, which provide rich nutritional support for glioblastoma (GBM). SENP1-mediated deSUMOylation stabilizes the expression of HIF1α and ß-catenin, leading to the occurrence of GSCs-initiated tumorigenesis. Targeting SENP1-mediated deSUMOylation may suppress the malignancy of GSCs and disrupt GBM progression. Methods: The expression of SENP1 in different World Health Organization grades was observed by immunohistochemistry and western blot. Lentivirus-packaged SENP1shRNA downregulated the expression of SENP1 in GSCs, and the downregulated results were verified by western blotting and polymerase chain reaction. The effects of LV-SENP1shRNA on the migration and proliferation of GSCs were detected by scratch and cloning experiments. The effect of LV-SENP1shRNA on the tumor formation ability of GSCs was observed in nude mice. Immunoprecipitation clarified the mechanism of SENP1 regulating the malignant behavior of GSCs under hypoxia. The correlation between the expression level of SENP1 and the survival of glioma patients was determined by statistical analysis. Results: SENP1 expression in GSCs derived from clinical samples was upregulated in GBM. SUMOylation was observed in GSCs in vitro, and deSUMOylation, accompanied by an increase in SENP1 expression, was induced by hypoxia. SENP1 expression was downregulated in GSCs with lentivirus-mediated stable transfection, which attenuated the proliferation and differentiation of GSCs, thus diminishing tumorigenesis. Mechanistically, HIF1α induced activation of Wnt/ß-catenin, which depended on SENP1-mediated deSUMOylation, promoting GSC-driven GBM growth under the hypoxia microenvironment. Conclusion: Our findings indicate that SENP1-mediated deSUMOylation as a feature of GSCs is essential for GBM maintenance, suggesting that targeting SENP1 against GSCs may effectively improve GBM therapeutic efficacy.

AdipoRon Ameliorates Synaptic Dysfunction and Inhibits tau Hyperphosphorylation through the AdipoR/AMPK/mTOR Pathway in T2DM Mice.

There is growing evidence showing that adiponectin (APN) can improve Alzheimer's disease(AD)-like pathological changes by improving insulin resistance. However, the role of AdipoRon (an Adiponectin receptor agonist) on synaptic plasticity and cognitive dysfunction in the early stages of type 2 diabetes mellitus(T2DM) remains unknown. In this study, we investigated the neuroprotective effect and the molecular mechanism underlying the effect of AdipoRon in T2DM mice. We found that AdipoRon significantly restored the cognitive deficits in T2DM mice, including shorter escape latency, more crossing times, increased distances, and percentage of time in the target quadrant. In addition, AdipoRon treatment up-regulated synaptic proteins (PSD95, SYN, GAP43, and SYP), increased the number of hippocampal synapses and attenuated synaptic damage, including the length, the number and the density of dendritic spines in CA1 and DG regions. Furthermore, AdipoRon attenuated Tau phosphorylation at multiple AD-related sites (p-tau 205, p-tau 396, p-tau 404) by promoting AdipoR expression and activating the AMPK/mTOR pathway. Our data suggests that AdipoRon exerts neuroprotective effects on the T2DM mice, which may be mediated by the activation of the AdipoR/AMPK/mTOR signaling pathway.

Computer-aided designing of a novel multi­epitope DNA vaccine against severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins--nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.

Study of Molecular Dimer Morphology Based on Organic Spin Centers: Nitronyl Nitroxide Radicals.

In this work, in order to investigate the short-range interactions between molecules, the spin-magnetic unit nitronyl nitroxide (NN) was introduced to synthesize self-assembly single radical molecules with hydrogen bond donors and acceptors. The structures and magnetic properties were extensively investigated and characterized by UV-Vis absorption spectroscopy, electron paramagnetic resonance (EPR), and superconducting quantum interference devices (SQUIDs). Interestingly, it was observed that the single molecules can form two different dimers (ring-closed dimer and "L"-type dimer) in different solvents, due to hydrogen bonding, when using EPR to track the molecular spin interactions. Both dimers exhibit ferromagnetic properties (for ring-closed dimer, J/kB = 0.18 K and ΔES-T = 0.0071 kcal/mol; for "L"-type dimer, the values were J/kB = 9.26 K and ΔES-T = 0.037 kcal/mol). In addition, the morphologies of the fibers formed by the two dimers were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM).

USP11 regulates proliferation and apoptosis of human spermatogonial stem cells via HOXC5-mediated canonical WNT/ß-catenin signaling pathway.

Spermatogonial stem cells (SSCs) are capable of transmitting genetic information to the next generations and they are the initial cells for spermatogenesis. Nevertheless, it remains largely unknown about key genes and signaling pathways that regulate fate determinations of human SSCs and male infertility. In this study, we explored the expression, function, and mechanism of USP11 in controlling the proliferation and apoptosis of human SSCs as well as the association between its abnormality and azoospermia. We found that USP11 was predominantly expressed in human SSCs as shown by database analysis and immunohistochemistry. USP11 silencing led to decreases in proliferation and DNA synthesis and an enhancement in apoptosis of human SSCs. RNA-sequencing identified HOXC5 as a target of USP11 in human SSCs. Double immunofluorescence, Co-immunoprecipitation (Co-IP), and molecular docking demonstrated an interaction between USP11 and HOXC5 in human SSCs. HOXC5 knockdown suppressed the growth of human SSCs and increased apoptosis via the classical WNT/ß-catenin pathway. In contrast, HOXC5 overexpression reversed the effect of proliferation and apoptosis induced by USP11 silencing. Significantly, lower levels of USP11 expression were observed in the testicular tissues of patients with spermatogenic disorders. Collectively, these results implicate that USP11 regulates the fate decisions of human SSCs through the HOXC5/WNT/ß-catenin pathway. This study thus provides novel insights into understanding molecular mechanisms underlying human spermatogenesis and the etiology of azoospermia and it offers new targets for gene therapy of male infertility.

Visualized in-sensor computing.

In artificial nervous systems, conductivity changes indicate synaptic weight updates, but they provide limited information compared to living organisms. We present the pioneering design and production of an electrochromic neuromorphic transistor employing color updates to represent synaptic weight for in-sensor computing. Here, we engineer a specialized mechanism for adaptively regulating ion doping through an ion-exchange membrane, enabling precise control over color-coded synaptic weight, an unprecedented achievement. The electrochromic neuromorphic transistor not only enhances electrochromatic capabilities for hardware coding but also establishes a visualized pattern-recognition network. Integrating the electrochromic neuromorphic transistor with an artificial whisker, we simulate a bionic reflex system inspired by the longicorn beetle, achieving real-time visualization of signal flow within the reflex arc in response to environmental stimuli. This research holds promise in extending the biomimetic coding paradigm and advancing the development of bio-hybrid interfaces, particularly in incorporating color-based expressions.