Insights into the hydrogen generation and catalytic mechanism on Co-based nanocomposites derived from pyrolysis of organic metal precursor.

Hydrogen generation from boron hydride is important for the development of hydrogen economy. Cobalt (Co) element has been widely used in the hydrolysis of boron hydride. Pyrolysis is a common method for materials synthesis in catalytic fields. Herein, Co-based nanocomposites derived from the pyrolysis of organic metal precursors and used for hydrolysis of boron hydride are summarized and discussed. The different precursors consisting of MOF, supported, metal, and metal phosphide precursors are summarized. The catalytic mechanism consisting of dissociation mechanism based on oxidative addition-reduction elimination, pre-activation mechanism, SN2 mechanism, four-membered ring mechanism, and acid-base mechanism is intensively discussed. Finally, conclusions and outlooks are conveyed from the design of high-efficiency catalysts, the characterization of catalyst structure, the enhancement of catalytic activities, the investigation of the catalytic mechanism, and the catalytic stability of active structure. This review can provide guidance for designing high-efficiency catalysts and boosting development of hydrogen economy.

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Effect of luteolin on glioblastoma's immune microenvironment and tumor growth suppression.

BACKGROUND: Glioblastoma is the most malignant and prevalent primary human brain tumor, and the immunological microenvironment controlled by glioma stem cells is one of the essential elements contributing to its malignancy. The use of medications to ameliorate the tumor microenvironment may give a new approach for glioma treatment. METHODS: Glioma stem cells were separated from clinical patient-derived glioma samples for molecular research. Other studies, including CCK8, EdU, Transwell, and others, supported luteolin's ability to treat glioma progenitor cells. Network pharmacology and molecular docking models were used to study the drug target, and qRT-PCR, WB, and IF were used to evaluate the molecular mechanism. Intracranial xenografts were examined using HE and IHC, while macrophage polarization was examined using FC. RESULTS: We originally discovered that luteolin inhibits glioma stem cells. IL6 released by glioma stem cells is blocked during medication action and inhibits glioma stem cell proliferation and invasion via the IL6/STAT3 signaling pathway. Additionally, luteolin inhibits the secretion of TGFß1, affects the polarization function of macrophages in the microenvironment, inhibits the polarization of M2 macrophages in TAM, and further inhibits various functions of glioma stem cells by affecting the IL6/STAT3 signaling pathway, luteolin crosstalk TGFß1/SMAD3 signaling pathway, and so on. CONCLUSIONS: Through the suppression of the immunological microenvironment and inhibition of the IL6/STAT3 signaling pathway, our study determined the inhibitory effect of luteolin on glioma stem cells. This medication's dual inhibitory action, which has a significant negative impact on the glioma stem cells' malignant process, makes it both a viable anti-glioma medication and a candidate for targeted glioma microenvironment therapy.

Role of lactate and lactate metabolism in liver diseases (Review).

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post­translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism­related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non­alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

Tuning Surface Organic Structures by Small Gas Molecules through Catassembly and Coassembly.

The field of molecular assembly has seen remarkable advancements across various domains, such as materials science, nanotechnology, and biomedicine. Small gas molecules serve as pivotal modulators, capable of altering the architecture of assemblies via tuning a spectrum of intermolecular forces including hydrogen bonding, dipole-dipole interactions, and metal coordination. Surface techniques, notably scanning tunneling microscopy and atomic force microscopy, have proven instrumental in dissecting the structural metamorphosis and characteristic features of these assemblies at an unparalleled single-molecule resolution. Recent research has spotlighted two innovative approaches for modulating surface molecular assemblies with the aid of small gas molecules: "catassembly" and "coassembly". This Perspective delves into these methodologies through the lens of varying molecular interaction types. The strategies discussed here for regulating molecular assembly structures using small gas molecules can aid in understanding various complex assembly processes and structures and provide guidance for the further fabrication of complex surface structures.

[Effect analysis of facial nerve decompression surgery in the treatment of Bell's palsy and Hunt syndrome].

Objective:To summarize and analyze the effect of facial nerve decompression surgery for the treatment of Bell's palsy and Hunt syndrome. Methods:The clinical data of 65 patients with facial nerve palsy who underwent facial nerve decompression in our center from October 2015 to October 2022 were retrospectively analyzed, including 54 patients with Bell's palsy and 11 patients with Hunter syndrome. The degree of facial paralysis（HB grade） was evaluated before surgery, and ENoG, pure tone audiometry, temporal bone CT and other examinations were completed. All patients had facial palsy with HB grade V or above after conservative treatment for at least 1 month, and ENoG decreased by more than 90%. All patients underwent facial nerve decompression surgery through the transmastoid approach within 3 months after onset of symptoms. The recovery effect of facial nerve function after surgery in patients with Bell's palsy and Hunter syndrome was summarized and analyzed. In addition, 15 cases in group A（operated within 30-60 days after onset） and 50 cases in group B（operated within 61-90 days after onset） were grouped according to the course of the disease（the interval between onset of symptoms and surgery） to explore the effect of surgical timing on postoperative effect. Results:There was no significant difference between the two groups of patients with Chi-square test（P=0.54） in 42 patients（77.8%, 42/54） with Bell's palsy and 7 patients（63.6%, 7/11） in patients with Hunter syndrome who recovered to grade Ⅰ-Ⅱ. According to the course of the disease, 10 cases（66.7%, 10/15） in group A recovered to grade Ⅰ-Ⅱ after surgery. In group B, 39 patients（78.0%, 39/50） recovered to grade Ⅰ-Ⅱ after surgery, and there was no statistically significant difference between the two groups by Chi-square test（P=0.58）. Conclusion:Patients with Bell's palsy and Hunter syndrome can achieve good results after facial nerve decompression within 3 months of onset, and there is no significant difference in the surgical effect between the two types of patients.

The role of anoctamin 1 in liver disease.

Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and hepatocellular carcinoma (HCC). Liver disease is now one of the leading causes of disease and death worldwide, which compels us to better understand the mechanisms involved in the development of liver diseases. Anoctamin 1 (ANO1), a calcium-activated chloride channel (CaCC), plays an important role in epithelial cell secretion, proliferation and migration. ANO1 plays a key role in transcriptional regulation as well as in many signalling pathways. It is involved in the genesis, development, progression and/or metastasis of several tumours and other diseases including liver diseases. This paper reviews the role and molecular mechanisms of ANO1 in the development of various liver diseases, aiming to provide a reference for further research on the role of ANO1 in liver diseases and to contribute to the improvement of therapeutic strategies for liver diseases by regulating ANO1.

Ginsenoside Rg5 inhibits glioblastoma by activating ferroptosis via NR3C1/HSPB1/NCOA4.

BACKGROUND: The utilization of Chinese medicine as an adjunctive therapy for cancer has recently gained significant attention. Ferroptosis, a newly regulated cell death process depending on the ferrous ions, has been proved to be participated in glioma stem cells inactivation. PURPOSE: We aim to study whether ginsenoside Rg5 exerted inhibitory effects on crucial aspects of glioma stem cells, including cell viability, tumor initiation, invasion, self-renewal ability, neurosphere formation, and stemness. METHODS: Through comprehensive sequencing analysis, we identified a compelling association between ginsenoside Rg5 and the ferroptosis pathway, which was further validated through subsequent experiments demonstrating its ability to activate this pathway. RESULTS: To elucidate the precise molecular targets affected by ginsenoside Rg5 in gliomas, we conducted an intersection analysis between differentially expressed genes obtained from sequencing and a database-predicted list of transcription factors and potential targets of ginsenoside Rg5. This rigorous approach led us to unequivocally confirm NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1) as a direct target of ginsenoside Rg5, a finding consistently supported by subsequent experimental investigations. Moreover, we uncovered NR3C1's capacity to transcriptionally regulate ferroptosis -related genes HSPB1 and NCOA4. Strikingly, ginsenoside Rg5 induced notable alterations in the expression levels of both HSPB1 (Heat Shock Protein Family B Member 1) and NCOA4 (Nuclear Receptor Coactivator 4). Finally, our intracranial xenograft assays served to reaffirm the inhibitory effect of ginsenoside Rg5 on the malignant progression of glioblastoma. CONCLUSION: These collective findings strongly suggest that ginsenoside Rg5 hampers glioblastoma progression by activating ferroptosis through NR3C1, which subsequently modulates HSPB1 and NCOA4. Importantly, this novel therapeutic direction holds promise for advancing the treatment of glioblastoma.

Adaptively resettable microfluidic patch for sweat rate and electrolytes detection.

Skin-interfaced microfluidic patch has become a reliable device for sweat collection and analysis. However, the intractable problems of emptying the microchannel for reuse, and the channel's volumetric capacity limited by the size of the patch, directly hinder the practical application of sweat sensors. Herein, we report an adaptively resettable microfluidic sweat patch (Art-Sweat patch) capable of continuously monitoring both sweat rate (0.2-4.0 µL min-1) and total ionic charge concentration (10-200 mmol L-1). We develop a platform with a vertical and horizontal microchannel combined strategy, enabling repeatedly filling sweat and emptying the microchannel for autonomously resetting and detecting. The variation in the emptied volume is designed to be adaptively identified by the sensor, resulting in enhanced stability and an enlarged volumetric capacity of over 300 µL. By integrating with self-designed wireless transmission modules, the proposed Art-Sweat patch shows product-level wearability and high performance in monitoring variations in regional sweat rate and concentration for hydration status assessment.

Steering Electron-Induced Surface Reaction via a Molecular Assembly Approach.

Electrons not only serve as a "reactant" in redox reactions but also play a role in "catalyzing" some chemical processes. Despite the significance and ubiquitousness of electron-induced chemistry, many related scientific issues still await further exploration, among which is the impact of molecular assembly. In this work, microscopic insights into the vital role of molecular assembly in tweaking the electron-induced surface chemistry are unfolded by combined scanning tunneling microscopy and density functional theory studies. It is shown that the selective dissociation of a C-Cl bond in 4,4″-dichloro-1,1':3',1''-terphenyl (DCTP) on Cu(111) can be efficiently triggered by an electron injection via the STM tip into the unoccupied molecular orbital. The DCTP molecules are embedded in different assembly structures, including its self-assembly and coassemblies with Br adatoms. The energy threshold for the C-Cl bond cleavage increases as more Br adatoms stay close to the molecule, indicative of the sensitive response of the electron-induced surface reactivity of the C-Cl bond to the subtle change in the molecular assembly. Such a phenomenon is rationalized by the energy shift of the involved unoccupied molecular orbital of DCTP that is embedded in different assemblies. These findings shed new light on the tuning effect of molecular assembly on electron-induced reactions and introduce an efficient approach to precisely steer surface chemistry.

Catalytically Active Carbon for Oxygen Reduction Reaction in Energy Conversion: Recent Advances and Future Perspectives.

The shortage and unevenness of fossil energy sources are affecting the development and progress of human civilization. The technology of efficiently converting material resources into energy for utilization and storage is attracting the attention of researchers. Environmentally friendly biomass materials are a treasure to drive the development of new-generation energy sources. Electrochemical theory is used to efficiently convert the chemical energy of chemical substances into electrical energy. In recent years, significant progress has been made in the development of green and economical electrocatalysts for oxygen reduction reaction (ORR). Although many reviews have been reported around the application of biomass-derived catalytically active carbon (CAC) catalysts in ORR, these reviews have only selected a single/partial topic (including synthesis and preparation of catalysts from different sources, structural optimization, or performance enhancement methods based on CAC catalysts, and application of biomass-derived CACs) for discussion. There is no review that systematically addresses the latest progress in the synthesis, performance enhancement, and applications related to biomass-derived CAC-based oxygen reduction electrocatalysts synchronously. This review fills the gap by providing a timely and comprehensive review and summary from the following sections: the exposition of the basic catalytic principles of ORR, the summary of the chemical composition and structural properties of various types of biomass, the analysis of traditional and the latest popular biomass-derived CAC synthesis methods and optimization strategies, and the summary of the practical applications of biomass-derived CAC-based oxidative reduction electrocatalysts. This review provides a comprehensive summary of the latest advances to provide research directions and design ideas for the development of catalyst synthesis/optimization and contributes to the industrialization of biomass-derived CAC electrocatalysis and electric energy storage.

Comprehensive analysis of the prognostic value and immunological role of IDO1 gene in pan-cancer.

OBJECTIVE: It has been demonstrated that IDO1, a target of immune checkpoint inhibition, functions as an oncogene in the majority of human malignancies. IDO1's function in human pan-cancers hasn't been thoroughly studied, though. MATERIALS AND METHODS: The Kaplan-Meier (K-M) and COX analyses were applied to the survival analysis. Furthermore, we used Spearman's correlation analysis to examine the associations between IDO1 and microsatellite instability (MSI), DNA methyltransferases (DNMTs), tumor mutational burden (TMB), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers. Moreover, immunohistochemical analysis and qRT-PCR were used to evaluate IDO1's expression in pan-cancer cells. RESULTS: The findings of this study reveal that IDO1 has abnormal expression in a number of malignancies and is related to the prognosis for UVM, LGG, KIRP, GBM, LAML, OV, READ, MESO, SARC, SKCM, and HNSC. Furthermore, the aberrant IDO1 expression was connected to the TMB, MSI, MMR, drug sensitivity, immune cells infiltrating, and tumor immune microenvironment across a variety of cancer types. The PCR results showed that in contrast to normal cells, IDO1 was found to be significantly highly expressed in breast cancer cells and hepatocellular carcinoma cells, and significantly lowly expressed in gastric cancer cells. CONCLUSION: The clinical treatment of IDO1 is now better supported by a theoretical basis and guidelines provided by our study.

Clinical Efficacy of Unilateral Dual-channel Endoscopic Lumbar Interbody Fusion for Lumbar Spondylolisthesis with Spinal Scoliosis.

OBJECTIVES: Scoliosis associated with spondylolisthesis is a common phenomenon. Recent research has reported that scoliosis can spontaneously disappear after lumbar spinal fusion surgery. Researchers have advocated that, for scoliosis associated with vertebral slippage, surgery for the latter may be the only necessary intervention, while unnecessary surgery for scoliosis should be avoided. So we propose that minimally invasive techniques can achieve treatment effects similar to those of open surgery. Therefore, in this study, we aimed to investigate the clinical efficacy of unilateral dual-channel endoscopic lumbar interbody fusion (ULIF) for treating lumbar spondylolisthesis with spinal scoliosis. METHODS: This study retrospectively analyzed patients with lumbar spondylolisthesis and spinal scoliosis who underwent ULIF between September 2021 and September 2023. Measurements of the Cobb angle, lumbar lordosis (LL) angle, sacral slope (SS), slip percentage (SP), slip angle (SA), L1 plumb line-S1 distance (LASD), and average intervertebral height (AIH) were taken preoperatively, immediately following surgery, 3 months after surgery, and at the final follow-up. The visual analogue scale (VAS), Oswestry disability index (ODI), and Japanese Orthopaedic Association (JOA) scoring systems were used to assess clinical results. The surgical efficacy was evaluated by comparing these parameters before and after surgery. Comparison of indicators within the same group was conducted using one-way repeated-measures analysis of variance or paired sample t-tests, whereas between-group differences were compared using an independent t-test. RESULTS: This study included 31 individuals who underwent surgery and completed follow-up. The follow-up period did not show a significant loss of corrective angles. Furthermore, the Cobb angle, SP, SA, and LASD significantly decreased after surgery, whereas the LL angle, SS, and AIH significantly increased (all p < 0.05). SP did not differ between the immediate postoperative period and the 3-month and final follow-up periods (p > 0.05). However, other parameters significantly improved during the follow-up period at all time points, except from 3 months to the final follow-up period (p > 0.05). Throughout the follow-up period, the lower back and leg pain VAS, ODI, and JOA scores considerably improved compared with the preoperative levels (p < 0.05). CONCLUSION: ULIF effectively treated lumbar spondylolisthesis with scoliosis, thereby reducing the degree of slip and scoliosis. By performing surgical reduction, fusion, and fixation only on the slipped segment, ULIF also had a corrective effect on the spinal lateral curvature, thereby avoiding the need for unnecessary scoliosis surgery. Moreover, the short-term efficacy was satisfactory, but the long-term efficacy requires further study.

Chromatin Modifier EP400 Regulates Oocyte Quality and Zygotic Genome Activation in Mice.

Epigenetic modifiers that accumulate in oocytes, play a crucial role in steering the developmental program of cleavage embryos and initiating life. However, the identification of key maternal epigenetic regulators remains elusive. In the findings, the essential role of maternal Ep400, a chaperone for H3.3, in oocyte quality and early embryo development in mice is highlighted. Depletion of Ep400 in oocytes resulted in a decline in oocyte quality and abnormalities in fertilization. Preimplantation embryos lacking maternal Ep400 exhibited reduced major zygotic genome activation (ZGA) and experienced developmental arrest at the 2-to-4-cell stage. The study shows that EP400 forms protein complex with NFYA, occupies promoters of major ZGA genes, modulates H3.3 distribution between euchromatin and heterochromatin, promotes transcription elongation, activates the expression of genes regulating mitochondrial functions, and facilitates the expression of rate-limiting enzymes of the TCA cycle. This intricate process driven by Ep400 ensures the proper execution of the developmental program, emphasizing its critical role in maternal-to-embryonic transition.

Efficacy and safety of Pien Tze Huang capsules in patients with herpes zoster: A multicenter, randomized, double-blinded, and placebo-controlled trial.

BACKGROUND: Herpes zoster (HZ) is a common medical condition accompanied by several distressing symptoms, including acute pain. Pien Tze Huang (PZH) is a well-known traditional Chinese medicine (TCM) with numerous pharmacological effects, including antiviral properties, neuroprotection, and immunity regulation. PURPOSE: To investigate the efficacy and safety of PZH capsules in patients with HZ. STUDY DESIGN: A multicenter, double-blinded, randomized, and placebo-controlled trial from 8 hospitals in 5 cities of China. METHODS: Eligible participants were randomly assigned to the PZH capsule and placebo group at a 1:1 ratio. Treatment was conducted for 14 days with a window period of no more than 2 days. For the first 7 days, participants received antiviral drugs combined with PZH capsules (0.6 g/time, 3 times a day) or placebos. For the remaining 7 days, they were only treated with PZH capsules (0.6 g/time, 3 times a day) or placebos. RESULTS: We included 222 patients in the full analysis set (FAS), and 187 patients in the per protocol set (PPS). The change of numeric rating scale pain scores from baseline to the seventh day (±1 day) after treatment in the PZH capsule group was statistically superior to the placebo group (FAS: 2.33 vs. 1.71, 97.5%CI: 0.03 ∼ 1.19; PPS: 2.29 vs. 1.51, 97.5%CI: 0.18 ∼ 1.38). In the PPS, there was a significant difference in the time (days) of pain relief between the placebo group and the PZH capsule group (Mean (SD): 5.71 (3.76) vs. 4.69 (3.57), p = 0.046). On the seventh day (±1 day) after treatment, the level of CD8+ cells in the PZH capsule group were higher than those of the placebo group (FAS: Mean (SD): 24.08 (6.81) vs. 21.93 (8.19), p = 0.007; PPS: Mean (SD): 24.26 (6.93) vs. 22.15 (8.51), p = 0.012). The level of cytotoxic lymphocyte cells found similar results on the seventh day (±1 day) (FAS: Mean (SD): 12.17 (4.65) vs. 10.55 (4.15), p = 0.018; PPS: Mean (SD): 12.25 (4.65) vs. 10.11 (3.93), p = 0.002). No serious adverse events were noted and PZH capsules were well tolerated. CONCLUSION: PZH capsules confer therapeutic effects on HZ with the TCM symptom of stagnated heat of liver channel by substantially reducing the pain intensity, shortening the time of pain relief as well as regulating the immune function. On the basis of the efficacy and safety profiles, PZH capsules may be a promising complementary therapy for the treatment of HZ.

Reforestation of Cunninghamia lanceolata changes the relative abundances of important prokaryotic families in soil.

Over the past decades, many forests have been converted to monoculture plantations, which might affect the soil microbial communities that are responsible for governing the soil biogeochemical processes. Understanding how reforestation efforts alter soil prokaryotic microbial communities will therefore inform forest management. In this study, the prokaryotic communities were comparatively investigated in a secondary Chinese fir forest (original) and a reforested Chinese fir plantation (reforested from a secondary Chinese fir forest) in Southern China. The results showed that reforestation changed the structure of the prokaryotic community: the relative abundances of important prokaryotic families in soil. This might be caused by the altered soil pH and organic matter content after reforestation. Soil profile layer depth was an important factor as the upper layers had a higher diversity of prokaryotes than the lower ones (p < 0.05). The composition of the prokaryotic community presented a seasonality characteristic. In addition, the results showed that the dominant phylum was Acidobacteria (58.86%) with Koribacteraceae (15.38%) as the dominant family in the secondary Chinese fir forest and the reforested plantation. Furthermore, soil organic matter, total N, hydrolyzable N, and NH4+-N were positively correlated with prokaryotic diversity (p < 0.05). Also, organic matter and NO3--N were positively correlated to prokaryotic abundance (p < 0.05). This study demonstrated that re-forest transformation altered soil properties, which lead to the changes in microbial composition. The changes in microbial community might in turn influence biogeochemical processes and the environmental variables. The study could contribute to forest management and policy-making.

Pharmacokinetics, pharmacodynamics and safety of 15 mg-tolvaptan administered orally for 7 consecutive days to Chinese patients with child-Pugh B cirrhosis.

Background: Tolvaptan, a selective vasopressin V2-receptor antagonist, can elicit a diuretic effect without significant electrolyte loss. The aims were to evaluate multiple-dose pharmacokinetics, pharmacodynamics and safety of daily administration of 15 mg tolvaptan in Chinese adult patients with confirmed Child-Pugh Class B cirrhosis accompanied by ascites. Methods: This was an open-label, single-center, single- and multiple-dose study. All patients received a daily 15 mg dose of tolvaptan for 7 consecutive days. The plasma concentrations of tolvaptan and its two metabolites (DM-4103, DM-4107) were measured using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). In addition, various pharmacokinetics parameters were calculated. The pharmacodynamic outcomes evaluated changes in serum sodium and potassium concentrations, daily urine volume, daily water consumption, fluid balance and body weight. Safety profiles, including the incidence of treatment-emergent adverse events (TEAEs), were carefully recorded. Results: Eleven patients with Child-Pugh B cirrhosis were eventually enrolled in the study. Plasma concentrations of tolvaptan and DM-4107 reached steady-states after 7 days of consecutive oral administration. No accumulation of tolvaptan or DM-4107 was found, but DM-4103 accumulated 18.2-fold after multiple-dosing. The daily urine volume and daily water consumption were statistically significantly increased after administration of tolvaptan from Day 1 to Day 7 (all p < 0.05), accompanied by an increased serum sodium concentration. Of 11 patients, 9 (81.8%) reported 20 TEAEs, with the majority being mild to moderate in severity. The most commonly occurring TEAEs were thirst (45.5%), pollakiuria (36.4%) and dry mouth (27.3%). Conclusion: Tolvaptan at a daily dose of 15 mg had a diuretic effect but did not increase serum sodium excretion or lead to tolvaptan accumulation. It is therefore can be safely used for short-term treatment of Chinese adult patients with confirmed Child-Pugh B cirrhosis. Clinical Trial Registration: https://clinicaltrials.gov/search?term=NCT01359462, identifier NCT01359462.

Research on stem cell therapy for spinal cord injury: a bibliometric and visual analysis from 2018-2023.

Objectives: The aim of this study was to conduct a bibliometric analysis of the literature on stem cell treatment for spinal cord injury to gain an intuitive understanding of how the field is progressing, discover topics of interest, and determine what development trends are emerging in this field. Background: Spinal cord injury and its complications often cause an enormous economic burden, and postinjury repair and treatment have always been challenging in clinical and scientific research. Stem cell therapy for spinal cord injury can prevent immune rejection and induce the release of neuroprotective and anti-inflammatory factors to reduce the production of stress-related proteins, reactive oxygen species, and inflammatory reactions. Methods: We analyzed the number and quality of publications in the field of stem cell therapy in spinal cord injury between 2018.01.01 and 2023.06.30 in the core collection database of Web of Science. CiteSpace and VOSviewer were used to sort and summarize these studies by country, institution, authors' publications, and collaborative networks. In addition, the research topics of interest were identified and summarized. Results: This study ultimately included 2,150 valid papers, with the number of publications showing a gradual upward trend. The country, institution, author and journal with the greatest number of publications and citations are China, the Chinese Academy of Sciences, Dai JW, and the International Journal of Molecular Sciences, respectively. The top three high-frequency keyword clusters were hereditary paraplegia, reactive astrocytes and tissue engineering. Conclusion: With the help of visual analysis, we identified general trends and research topics of interest in the field of spinal cord injury over the last 5 years. Our findings suggest that stem cell transplantation for spinal cord injury and exosome therapy may be a focus of future research. This study provides a foundation for future research on stem cell therapy as well as clinical efforts in this field.

A Comprehensive Pan-cancer Analysis of the Biological Immunomodulatory Function and Clinical Value of CD27.

Background: CD27 is an immunological checkpoint gene, plays a critical function inInhibition or activation of cancer immunity. The CD27/CD27L axis is its pathway of action. Therefore, our goal was to examine the predictive role of CD27 in the clinical prognosis of 33 cancer types and its functions in cancer progression, as well as explore the link between pan-cancer CD27 gene expression and immune infiltration. Methods: By comprehensive use of datasets and methods from TCGA, cBioPortal, GTEx, HPA, KM-plotter, Spearman, CellMinerTM, R packages and RT-qPCR, we delved deeper into the potential impact of the CD27 on cancer development. These include expression differences, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways, TMB, MSI, and prognosis. Also, we explored CD27 interactions with different drugs. Results: The results showed that, mutated CD27 was highly expressed in most cancers. The CD27 showed strong diagnostic value in 4 cancers and marked a positive prognosis for CESC, intracervical adenocarcinoma, HNSC, and endometrial cancer, and a poor prognosis for UVM. In addition, CD27 affects multiple immune and inflammatory signaling pathways and is positively correlated with immune cell infiltration, T cell differentiation, macrophage M1 polarization, stromal infiltration, and drug sensitivity. DNA methylation is involved in CD27 expression in cancer. Conclusion: CD27, which is mutated in cancers and appears widely highly expressed and altered tumor immune invasion and stromal invasion by affecting multiple immune-related and inflammation signaling pathways, plays a significant role in CESC, HNSC, UCEC and UVM, and may be used as a therapeutic target for related cancers.

Surface-confined alternating copolymerization with molecular precision by stoichiometric control.

Keen desires for artificial mimicry of biological polymers and property improvement of synthesized ones have triggered intensive explorations for sequence-controlled copolymerization. However, conventional synthesis faces great challenges to achieve this goal due to the strict requirements on reaction kinetics of comonomer pairs and tedious synthetic processes. Here, sequence-controlled alternating copolymerization with molecular precision is realized on surface. The stoichiometric control serves as a thermodynamic strategy to steer the polymerization selectivity, which enables the selective alternating organometallic copolymerization via intermolecular metalation of 4,4"-dibromo-p-terphenyl (P-Br) and 2,5-diethynyl-1,4-bis(phenylethynyl)benzene (A-H) with Ag adatoms on Ag(111) at P-Br: A-H = 2, as verified by scanning tunneling microscopy and density functional theory studies. In contrast, homopolymerization yield increases as the stoichiometric ratio deviates from 2. The microscopic characterizations rationalize the mechanism, providing a delicate explanation of the stoichiometry-dependent polymerization. These findings pave a way to actualizing an efficient sequence control of copolymerization by surface chemistry.