Review on synthetic approaches and PEC activity performance of bismuth binary and mixed-anion compounds for potential applications in marine engineering.

Photoelectrochemical (PEC) technology in marine engineering holds significant importance due to its potential to address various challenges in the marine environment. Currently, PEC-type applications in marine engineering offer numerous benefits, including sustainable energy generation, water desalination and treatment, photodetection, and communication. Finding novel efficient photoresponse semiconductors is of great significance for the development of PEC-type techniques in the marine space. Bismuth-based semiconductor materials possess suitable and tunable bandgap structures, high carrier mobility, low toxicity, and strong oxidation capacity, which gives them great potential for PEC-type applications in marine engineering. In this paper, the structure and properties of bismuth binary and mixed-anion semiconductors have been reviewed. Meanwhile, the recent progress and synthetic approaches were discussed from the point of view of the application prospects. Finally, the issues and challenges of bismuth binary and mixed-anion semiconductors in PEC-type photodetection and hydrogen generation are analyzed. Thus, this perspective will not only stimulate the further investigation and application of bismuth binary and mixed-anion semiconductors in marine engineering but also help related practitioners understand the recent progress and potential applications of bismuth binary and mixed-anion compounds.

Driving force of value reversal in Chinese overleveraged firms: The mechanism and path of private placement.

To stimulate economic growth, China has launched multiple economic stimulus plans in recent years, intensifying corporate debt financing and subsequently elevating the leverage levels. Addressing and effectively reducing the leverage levels of our country's enterprises has emerged as a pressing issue in the trajectory of our economic development. This paper primarily investigates the drivers, pathways, and mechanisms for reversing the over-leveraged values of enterprises. Key findings include: (1) Excessive indebtedness exerts a negative impact on corporate value, with the suppressing effect intensifying as the degree of over-leverage increases; (2) Over-leveraged enterprises can effectively decrease their debt levels and enhance their value through private placement. Further research suggests that this mechanism operates by amplifying the operational leverage of over-leveraged enterprises post private placement and alleviating financing constraints, thereby elevating corporate value. (3) Compared to non-state-owned enterprises, state-owned enterprises exhibit higher levels of indebtedness. Among over-leveraged firms, enhancements in corporate governance and increased investment efficiency can positively transform corporate value. This study offers valuable insights for the ongoing supply-side structural reforms and governance guidance from the regulatory bodies.

Clinical applications of metagenomic next-generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study.

BACKGROUND: This study aimed to evaluate the application of metagenomic next-generation sequencing (mNGS) technology to identify pathogens in periprosthetic joint infection (PJI). METHODS: A retrospective analysis was conducted on 65 patients suspected of having PJI between April 2020 and July 2023. The patients were categorized into PJI (46 patients) and non-PJI (19 patients) groups based on the 2018 International Consensus Meeting criteria. Clinical data were collected, and both conventional bacterial culture and mNGS were performed. The diagnostic performance of the two methods was compared and analyzed. RESULTS: mNGS exhibited a sensitivity of 89.13%, a specificity of 94.74%, a positive predictive value of 97.62%, a negative predictive value of 78.26%, and an overall diagnostic accuracy of 90.77%. Compared to microbial culture, mNGS demonstrated superior diagnostic sensitivity while maintaining similar specificity. A total of 48 pathogens were successfully identified using mNGS, with Coagulase-negative staphylococci, Streptococci, Staphylococcus aureus, and Cutibacterium acnes being the most common infectious agents. Notably, mNGS was used to identify 17 potential pathogens in 14 culture-negative PJI samples, highlighting its ability to detect rare infectious agents, including Cutibacterium acnes (n = 5), Granulicatella adiacens (n = 1), Mycobacterium tuberculosis complex (n = 1), and Coxiella burnetii (n = 1), among others, which are not detectable by routine culture methods. However, mNGS failed to detect the pathogen in 4 culture-positive PJI patients, indicating its limitations. Among the 46 PJI patients, 27 had positive culture and mNGS results. The results of mNGS were concordant with those of culture at the genus level in 6 patients with PJI and at the species level in 18 patients. Furthermore, the present study revealed a significantly greater proportion of Staphylococcus aureus in the sinus tract group (45.45%) than in the non-sinus tract group (14.29%), indicating the association of this pathogen with sinus formation in PJI (P = 0.03). Additionally, there was no significant difference in the occurrence of polymicrobial infections between the sinus tract group (27.27%) and the non-sinus tract group (33.33%) (P = 0.37). CONCLUSIONS: Metagenomic next-generation sequencing can serve as a valuable screening tool in addition to traditional culture methods to improve diagnostic accuracy through optimized culture strategies.

High-performance asymmetric supercapacitors assembled with novel disc-like MnCo2O4 microstructures as advanced cathode material.

Herein, porous MnCo2O4 with disc-like (MnCo2O4-discs) and ring-like (MnCo2O4-rings) microstructures were respectively synthesized using an initial hydrothermal method at different temperatures and a calcination treatment in air. The electrochemical properties of these MnCo2O4 materials were investigated in three-electrode and two-electrode systems, and as such, MnCo2O4 presented a battery-like electrochemical response. The specific capacity of MnCo2O4-discs was determined to be 296.1C/g at 1 A/g, superior to 246.3C/g for MnCo2O4-rings. An asymmetric supercapacitor (ASC) was assembled with MnCo2O4 as the cathode and activated carbon (AC) as the anode to evaluate the potential for practical application. The MnCo2O4-discs//AC ASC exhibited an energy density (Ed) of 35.8 W h kg-1 at a power density (Pd) of 927.5 W kg-1. For the MnCo2O4-rings//AC ASC, an inferior Ed of 31.4 W h kg-1 under 890.9 W kg-1 was achieved. Furthermore, the two ASCs presented outstanding cyclic performance after 5000 cycles at 6 A/g. The exceptional properties of MnCo2O4 microstructures can be applied to the assembly of ASC devices, which can have promising potential for application in electrochemical energy storage. This synthetic method is straightforward, cost-effective, and can be extended to fabricate similar electrode materials with superior electrochemical performance.

Sonochemical synthesis of CoNi layered double hydroxide as a cathode material for assembling high performance hybrid supercapacitor.

Fabricating battery-type electrode materials with large specific surface area and mesopores is an efficient method for enhancing the electrochemical performance of supercapacitors. This method may provide more active sites for Faradic reactions and shorten the ion-diffusion paths. In this study, the CoNi layered double hydroxides (LDHs) with the morphology of nanoflowers and nanoflakes were prepared in solutions with pH values of 7.5 (CoNi LDH-7.5) and 8.5 (CoNi LDH-8.5) via a simple sonochemical approach. These CoNi LDHs possessed large specific surface areas and favourable electrochemical properties. The CoNi LDH-7.5 delivered a specific capacity of 740.8C/g at a current density of 1 A/g, surpassing CoNi LDH-8.5 with 668.1C/g. The hybrid supercapacitor (HSC) was assembled with activated carbon as the anode and CoNi LDH as the cathode to assess its practical application potential in the field of electrochemical energy storage. The CoNi LDH-7.5//AC HSC achieved the highest energy density of 35.6 W h kg-1 at a power density of 781.1 W kg-1. In addition, both HSCs exhibited little capacity decay over 5,000 cycles at a high current load of 8 A/g. These electrochemical properties of CoNi LDHs make them promising candidates for battery-type electrode materials. The current sonochemical method is simple and can be applied to the preparation of other LDHs-based electrode materials with favourable electrochemical performance.

[Primary Structure Characterization and Biosynthesis of Spider Silk Proteins for Multifunctional Biomaterials].

Spider silk is a natural fiber known as "biosteel" with the strongest composite performance, such as high tensile strength and toughness. It is also equipped with excellent biocompatibility and shape memory ability, thus shows great potential in many fields such as biomedicine and tissue engineering. Spider silk is composed of macromolecular spidroin with rich structural diversity. The characteristics of the primary structure of natural spidroin, such as the high repeatability of amino acids in the core repetitive region, the high content of specific amino acids, the large molecular weight, and the high GC content of the spidroin gene, have brought great difficulties in heterologous expression. This review discusses focuses on the relationship between the featured motifs of the microcrystalline region in the repetitive unit of spidroin and its structure, as well as the spinning performance and the heterologous expression. The optimization design for the sequence of spidroin combined with heterologous expression strategy has greatly promoted the development of the biosynthesis of spider silk proteins. This review may facilitate the rational design and efficient synthesis of recombinant spidroin.

M2 macrophage­derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL­1 myocytes via the NF­κB (p65)/STAT3 signaling pathway.

The present study was designed to explore the role of M2 macrophage­derived exosomes (M2­exos) on the KCa3.1 channel in a cellular atrial fibrillation (AF) model using rapidly paced HL­1 myocytes. M2 macrophages and M2­exos were isolated and identified. MicroRNA (miR)­146a­5p levels in M2 macrophages and M2­exos were quantified using reverse transcription­quantitative PCR (RT­qPCR). HL­1 myocytes were randomly divided into six groups: Control group, pacing group, pacing + coculture group (pacing HL­1 cells cocultured with M2­exos), pacing + mimic­miR­146a­5p group, pacing + NC­miR­146a­5p group and pacing + pyrrolidine dithiocarbamate (PDTC; a special blocker of the NF­κB signaling pathway) group. Transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT­qPCR and immunohistochemistry were performed in the present study. A whole­cell clamp was also applied to record the current density of KCa3.1 and action potential duration (APD) in each group. The results revealed that miR­146a­5p was highly expressed in both M2 macrophages and M2­exos. Pacing HL­1 cells led to a shorter APD, an increased KCa3.1 current density and higher protein levels of KCa3.1, phosphorylated (p­)NF­κB p65, p­STAT3 and IL­1ß compared with the control group. M2­exos, miR­146a­5p­mimic and PDTC both reduced the protein expression of KCa3.1, p­NF­κB p65, p­STAT3 and IL­1ß and the current density of KCa3.1, resulting in a longer APD in the pacing HL­1 cells. In conclusion, M2­exos and their cargo, which comprised miR­146a­5p, decreased KCa3.1 expression and IL­1ß secretion in pacing HL­1 cells via the NF­κB/STAT3 signaling pathway, limiting the shorter APD caused by rapid pacing.

METTL3 modification of circStk4 affects mouse glomerular messangial cell autophagy, proliferation and apotosis by regulating miR-133a-3p/C1 axis.

OBJECTIVE: The study aimed to explore the impact of N6-methyladenosine (m6A) modification in circStk4 on glomerular mesangial cells (GMCs) autophagy, proliferation and apoptosis. METHODS: The interactions between circStk4 and miR-133a-3p, miR-133a-3p and C1 were demonstrated through luciferase reporter assays. The circStk4 localization was analyzed using fluorescence in situ hybridization and nuclear/cytosol fractionation assays. Colorimetric assays, MeRIP-qPCR, and western blot (WB) were employed to confirm the m6A modification of circStk4 and identify the key methylation enzyme. RT-qPCR was conducted to determine the impact of METTL3 on the circStk4 RNA expression. Additionally, CCK-8, flow cytometry, transmission electron microscopy, immunofluorescence, WB and RT-qPCR were employed to investigate the effects of METTL3 or circStk4 on the proliferation, autophagy and apoptosis of GMCs. Enzyme-linked immunosorbent assay was utilized to assess the inflammatory factors. RESULTS: m6A modifications were found in circStk4 and METTL3 was a key methylating enzyme. Furthermore, it was observed that circStk4 competitively bound miR-133a-3p and increased C1 levels. Silencing circStk4 resulted in decreased GMCs proliferation, increased autophagy and apoptosis, and reduced inflammation levels. Additionally, METTL3 played a role in inhibiting GMCs proliferation and promoting autophagy and apoptosis by regulating the circStk4 expression. On verifying the interplay between autophagy, proliferation and apoptosis, and found that the inhibition of autophagy led to an increase in cell proliferation and a decrease in apoptosis. CONCLUSION: m6A modification of circStk4 mediated by METTL3 influenced circStk4 expression and impacted autophagy, proliferation and apoptosis in GMCs via the miR-133a-3p/C1 axis. This discovery introduces a novel therapeutic approach for CGN treatment.

Assessment of early scientific research skills training for medical undergraduates in China.

The medical field is facing a physician-scientist shortage, threatening future medical research and development. Medical institutions can contribute to developing physician-scientists by stimulating students' involvement in research. In this study, a medical undergraduate teaching module to develop research skills and encourage interest in research was held in Chongqing, China. Undergraduate medical students at Chongqing Medical University completed research skills training. Before and after the training, an online, anonymous, self-reported questionnaire was administered. The self-reported questionnaire investigated students' demographic characteristics, students' perception of attitudes toward conducting research, research skills (e.g., identifying and utilizing information, critical appraisal of literature, paper writing, and understanding of research), and feedback on scientific research training. The module was implemented with 25 students from July 2019 to October 2019, and 96.0% (N = 24) of participants responded to the questionnaire both prior to and after the training. In the evaluation of research skills, results showed that use of appropriate tools for research (Z = -3.340, p < 0.01), students' ability to undertake a focused literature search (Z = -3.40, p < 0.01), identifying and utilizing information (Z = -3.34, p < 0.01), and paper-writing skills (Z = -3.49, p < 0.01) were significantly improved after the undergraduates participated in the scientific research training. A qualitative analysis of the feedback showed that students found that the training helped to enhance their knowledge, improve their study scores, and motivate them to conduct research in the future. Early scientific research ability training strengthened the research skills of medical undergraduates and motivated them to pursue research.

Long-term management and treatment of acute intermittent porphyria with recurring attacks using pharmacological prophylaxis.

BACKGROUND: There is no definitive guidance on whether patients with acute intermittent porphyria (AIP) with recurrent attacks need pharmacological prophylactic treatment. METHODS: The management strategies for patients with frequent (defined as ≥4 annualized attack rate (AAR) and less frequent attacks (<4 AAR), including treatment for acute attacks and duration of prophylaxis (weekly heme arginate 3 mg/kg body weight and/or investigational drug, givosiran), were summarized. The AAR for the following periods were presented: the first 2 years after diagnosis, before/after prophylaxis, and the most recent 2 years. RESULTS: A total of 29 patients with AIP were included, 19 (34.5%) had <4 AAR and 10 (65.6%) had ≥4 AAR in the first 2 years after diagnosis. All patients experienced reduced attacks during the treatment course, 23 (79.3%) were attack-free during the most recent 2 years. Among the 9 patients who received prophylaxis (7 heme arginate; 1 givosiran, 1 heme arginate followed by givosiran), 5 (55.6%) were attack-free in the most recent 2-year period and prophylaxis was discontinued because there had been no attacks for >1 year. For patients without prophylaxis (n = 20), 18 (90.0%) were attack-free in the most recent 2-year period and 15 (75.0%) experienced attacks only in the first 2 years after diagnosis. CONCLUSIONS: Prophylaxis could be considered for patients with AIP with ≥4 biochemically confirmed attacks/year after routine treatment of 1-2 years, during which the severity and frequency of attacks should be closely monitored to determine the necessity of pharmacologic prophylaxis. More studies are needed to reach a consensus on the use of pharmacological prophylaxis and treatment of AIP.

Association of Alternative Dietary Patterns with Osteoporosis and Fracture Risk in Older People: A Scoping Review.

PURPOSE: Although the Mediterranean diet has been associated with a lower risk of hip fracture, the effect of other dietary patterns on bone density and risk of fracture is unknown. This scoping review aims to investigate the association between adherence to alternative dietary patterns (other than the traditional Mediterranean diet) and osteoporosis or osteoporotic fracture risk in older people. METHODS: A systematic search was carried out on three electronic databases (Medline, EMBASE, and Scopus) to identify original papers studying the association between alternative dietary patterns (e.g., Baltic Sea Diet (BSD), modified/alternative Mediterranean diet in non-Mediterranean populations, Dietary Approaches to Stop Hypertension (DASH)) assessed using 'prior' methods (validated scores) and the risk of osteoporotic fracture or Bone Mineral Density (BMD) in people aged ≥50 (or reported average age of participants ≥ 60). Results from the included studies were presented in a narrative way. RESULTS: Six observational (four prospective cohort and two cross-sectional) studies were included. There was no significant association between BMD and BSD or DASH scores. Higher adherence to DASH was associated with a lower risk of lumbar spine osteoporosis in women in one study, although it was not associated with the risk of hip fracture in another study with men and women. Higher adherence to aMED (alternative Mediterranean diet) was associated with a lower risk of hip fracture in one study, whereas higher adherence to mMED (modified Mediterranean diet) was associated with a lower risk of hip fracture in one study and had no significant result in another study. However, diet scores were heterogeneous across cohort studies. CONCLUSIONS: There is some evidence that a modified and alternative Mediterranean diet may reduce the risk of hip fracture, and DASH may improve lumbar spine BMD. Larger cohort studies are needed to validate these findings.

Progress on Z genome biosynthetic pathway of bacteriophage.

There are abundant base modifications in bacteriophages' genomes, mainly for avoiding the digestion of host endonucleases. More than 40 years ago, researchers discovered that 2-amino-adenine (Z) completely replaced adenine (A) and forms a complementary pairing with three hydrogen bonds with thymine (T) in the DNA of cyanophage S-2L, forming a distinct "Z-genome". In recent years, researchers have discovered and validated the biosynthetic pathway of Z-genome in various bacteriophages, constituting a multi-enzyme system. This system includes the phage-encoded enzymes deoxy-2'-aminoadenylosuccinate synthetase (PurZ), deoxyadenosine triphosphate hydrolase (dATPase/DatZ), deoxyadenosine/deoxyguanosine triphosphate pyrophosphatase (DUF550/MazZ) and DNA polymerase (DpoZ). In this review, we provide a concise overview of the historical discovery on diversely modified nucleosides in bacteriophages, then we comprehensively summarize the research progress on multiple enzymes involved in the Z-genome biosynthetic pathway. Finally, the potential applications of the Z-genome and the enzymes in its biosynthetic pathway are discussed in order to provide reference for research in this field.

Is Sliding Compression Necessary for Intramedullary Nailing Fixation of AO/OTA Type A3.3 Intertrochanteric Fracture?

OBJECTIVES: The intramedullary nail is considered the gold standard for treating AO/OTA type A3.3 intertrochanteric fractures. However, it still faces a significant rate of failure, mainly due to the critical factor of comminuted lateral wall defects leading to inadequate proximal sliding compression. The primary objective of this study is to investigate the requirement of sliding compression in the treatment of unstable AO/OTA type A3.3 intertrochanteric fractures. To achieve this, we conduct a comparative analysis between two approaches: InterTAN alone and proximal femoral anti-rotation blade nailing (PFNA) combined with lateral wall reconstruction for treating AO/OTA type A3.3 intertrochanteric fractures with lateral wall damage. METHODS: A retrospective analysis was conducted on the clinical data of patients who underwent intramedullary nailing fixation for AO/OTA type A3.3 intertrochanteric fractures at our hospital from January 2012 to January 2022. Patient characteristics as well as treatment details, including operative time, intraoperative blood loss, weight-bearing time, fracture healing time, tip apex distance (TAD) loss, Harris hip scores (HHS), Parker-Palmer mobility score (PPMS), and postoperative complications, were collected and analyzed. Continuous variables were analyzed using independent sample t-tests, while categorical variables were examined using the chi-square test. For group comparisons, variance analysis was applied, and pairwise comparisons were conducted using the LSD-t test. RESULTS: These patients were divided into PFNA combined with lateral wall reconstruction group (sliding compression group) and InterTAN fixation group (static fixation group) based on surgical methods. The operation time, intraoperative bleeding loss, HHS at 12 months and PPMS at 12 months in the sliding compression group were significantly higher than those in the static fixation group, and time to weight-bearing and fracture healing time were significantly lower than those in the static fixation group (p < 0.05). There were no significant differences between two groups in terms of the TAD at 2 days, 2, and 12 months postoperatively, the incidence of complications (p > 0.05). At 6 months postoperatively, femoral neck length was shortened compared to 2 days postoperatively in both groups, and the sliding compression group had a significantly greater degree of femoral neck shortening than the static fixation group (p < 0.05). CONCLUSION: The use of PFNA with lateral wall reconstruction for A3.3 intertrochanteric fractures demonstrated superior mobility, efficiency, and reduced internal fixation failure rates compared to InterTAN. These findings suggest that sliding compression may be required for intramedullary nailing treatment.

Risk of Thrombosis Following the First Dose of ChAdOx1 nCoV-19 Vaccine in Patients Undergoing Maintenance Hemodialysis: A Self-Controlled Case Series Study.

Background: The ChAdOx1 nCoV-19 vaccine is associated with vaccine-induced thrombosis and thrombocytopenia (VITT). Patients with end-stage renal disease (ESRD) under hemodialysis are at elevated risk of heparin-induced thrombocytopenia, which shares similar mechanisms with VITT. We aimed to examine the risk of VITT after the first dose of ChAdOx1 nCoV-19 vaccine using a self-controlled case series analysis (SCCS) in the hemodialyzed ESRD population. Methods: Drawing from the largest multi-center electronic medical records database in Taiwan, we identified adult patients, with or without hemodialysis, between 1st December, 2020, and 31st December, 2021, who received a first dose of ChAdOx1 nCoV-19 vaccine and had an outcome of thrombocytopenia, venous thrombosis, or arterial thrombosis. We calculated the incident rate ratios (IRRs) of outcomes in different periods at risk, compared to periods not at risk. Results:  We identified 59 hemodialysis patients and 41 non-dialysis patients with an outcome. The SCCS analyses showed, for the hemodialysis group, a significantly increased risk of outcomes during the period 31 to 60 days post-exposure to ChAdOx1 nCoV-19 vaccine (IRR: 2.823; 95% CI: 1.423-5.600). However, in non-dialysis patients there was no increase in risks during any of the post-exposure risk periods. Conclusion: For ESRD patients under hemodialysis, the first dose of ChAdOx1 nCoV-19 vaccine was associated with a 2.8-fold increase in risk of thrombosis.

Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study.

OBJECTIVE: To investigate the associations between exposure to antenatal corticosteroids and serious infection in children during the first three, six, and 12 months of life. DESIGN: Nationwide cohort study. SETTING: National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database, 1 January 2008 to 31 December 2019, to identify all pregnant individuals and their offspring in Taiwan. PARTICIPANTS: 1 960 545 pairs of pregnant individuals and their singleton offspring. 45 232 children were exposed and 1 915 313 were not exposed to antenatal corticosteroids. MAIN OUTCOME MEASURES: Incidence rates were estimated for overall serious infection, sepsis, pneumonia, acute gastroenteritis, pyelonephritis, meningitis or encephalitis, cellulitis or soft tissue infection, septic arthritis or osteomyelitis, and endocarditis during the first three, six, and 12 months of life in children exposed versus those not exposed to antenatal corticosteroids. Cox proportional hazards models were performed to quantify adjusted hazard ratios with 95% confidence intervals for each study outcome. RESULTS: The study cohort was 1 960 545 singleton children: 45 232 children were exposed to one course of antenatal corticosteroids and 1 915 313 children were not exposed to antenatal corticosteroids. The adjusted hazard ratios for overall serious infection, sepsis, pneumonia, and acute gastroenteritis among children exposed to antenatal corticosteroids were significantly higher than those not exposed to antenatal corticosteroids during the first six months of life (adjusted hazard ratio 1.32, 95% confidence interval 1.18 to 1.47, P<0.001, for overall serious infection; 1.74, 1.16 to 2.61, P=0.01, for sepsis; 1.39, 1.17 to 1.65, P<0.001, for pneumonia; and 1.35, 1.10 to 1.65, P<0.001, for acute gastroenteritis).Similarly, the adjusted hazard ratios for overall serious infection (P<0.001), sepsis (P=0.02), pneumonia (P<0.001), and acute gastroenteritis (P<0.001) were significantly higher from birth to 12 months of life. In the sibling matched cohort, the results were comparable with those observed in the whole cohort, with a significantly increased risk of sepsis in the first six (P=0.01) and 12 (P=0.04) months of life. CONCLUSIONS: This nationwide cohort study found that children exposed to one course of antenatal corticosteroids were significantly more likely to have an increased risk of serious infection during the first 12 months of life. These findings suggest that before starting treatment, the long term risks of rare but serious infection associated with antenatal corticosteroids should be carefully weighed against the benefits in the perinatal period.

Identification of Rab7 as an autophagy marker: potential therapeutic approaches and the effect of Qi Teng Xiao Zhuo granule in chronic glomerulonephritis.

CONTEXT: Qi Teng Xiao Zhuo granule (QTXZG) is a traditional Chinese medicine (TCM) used for therapeutic effects on chronic glomerulonephritis (CGN). However, the underlying mechanism remains unclear. OBJECTIVE: To investigate the molecular mechanism of QTXZG on CGN by proteomics. MATERIALS AND METHODS: The CGN model was induced in Sprague-Dawley rats by injecting adriamycin (3.5 mg/kg, Day 1; 3.0 mg/kg, Day 14) twice through the tail vein. Urine samples were collected on the 21st day; and the rats divided randomly into control, adriamycin, QTXZG administration groups. Rats in the QTXZG group received QTXZG (10.8 g/kg); control and adriamycin groups were given physiological saline once per day for 30 days. Proteomics was applied to identify the candidate proteins combined with autophagy database and verified by immunofluorescence (IF) and western blots (WB). RESULTS: 278 differentially expressed proteins (DEPs) were identified based on proteomics and Rab7 was screened as an autophagy protein biomarker. In vitro cell experiments, we found that QTXZG (20%, IC50 = 23.47%) could decrease the expression of NLRP3, Caspase-1, IL-18, IL-1ß, while increasing the expression of Pink1, Parkin, Rab7, Podocalyxin. The cell apoptosis rate increased from 6.68 ± 0.07 to 11.03 ± 0.36%. Overexpression of Rab7 resulted in an increase in autophagy relevant protein expression. DISCUSSION AND CONCLUSION: TCM CGN-regulating herbs (QTXZG) can exert therapeutic effects by affecting the Rab7/Pink1/Parkin pathway to promote mitochondrial autophagy. New breakthroughs in targeted Rab7 may eventually enable such applications.

Efficacy of epidural analgesia for intractable cancer pain: A systematic review.

BACKGROUND: Epidural analgesia is a common technique for managing perioperative and obstetric pain. Patients with cancer who cannot tolerate opioids or not responding to conventional treatment may benefit from epidural analgesia. Therefore, this systematic review aimed to analyze the efficacy and safety of epidural analgesia in patients with intractable cancer pain. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify studies on patients with cancer who received epidural analgesia. We assessed the quality of all included studies using the risk-of-bias tool or Newcastle-Ottawa scale. The primary outcome was pain relief after epidural analgesia, and the secondary outcome was quality of life, analgesic consumption, and adverse events. The studies were grouped based on the medications used for epidural analgesia. A descriptive synthesis was performed following the Synthesis Without Meta-analysis reporting guideline. RESULTS: Our systematic review included nine randomized controlled trials (n = 340) and 15 observational studies (n = 926). Two randomized controlled trials suggested that epidural opioids were not superior to systemic opioids in relieving pain. Epidural opioids combined with local anesthetics or adjuvants, including calcitonin, clonidine, ketamine, neostigmine, methadone, and dexamethasone, offered better analgesic effects. No significant difference in pain relief between an intermittent bolus and a continuous infusion of epidural morphine was observed. Epidural opioids had more analgesic effects on nociceptive pain than neuropathic pain. The methods used to evaluate the quality of life and the corresponding results were heterogeneous among studies. Six observational studies demonstrated that some patients could have decreased opioid consumption after epidural analgesia. Adverse events, including complications and drug-related side effects, were reported in 23 studies. Five serious complications, such as epidural abscess and hematoma, required surgical management. The heterogeneity and methodological limitations of the studies hindered meta-analysis and evidence-level determination. CONCLUSION: Coadministration of epidural opioids, local anesthetics, and adjuvants may provide better pain relief for intractable cancer pain. However, we must assess the patients to ensure that the benefits outweigh the risks before epidural analgesia. Therefore, further high-quality studies are required.

Factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment: A real-world experience.

PURPOSE: The aim of this study was to investigate the factors predictive of clinical outcome in advanced hepatocellular carcinoma patients receiving ramucirumab treatment. METHODS: We conducted a retrospective study using a multi-institutional electronic medical records database in Taiwan. We included advanced HCC patients newly receiving ramucirumab as second-line or beyond systemic therapy between January 2016 and February 2022. The clinical outcomes were median progression-free survival (PFS) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST), overall survival (OS) and adverse events. We applied Kaplan-Meier methods to estimate median PFS and OS. Uni-variable and multi-variable Cox regression models were applied to identify the prognostic factors. RESULTS: We included 39 ramucirumab naive users with a median age of 65.5 (IQR: 57.0-71.0) years and treatment time of 5.0 (3.0-7.0) cycles, of whom 82.1% were male and 84.6% were Barcelona Clinic Liver Cancer (BCLC) stage C. After median follow-up time of 6.0 months, 33.3% of patients' AFP level had decreased more than 20% within 12 weeks. The median PFS and OS were 4.1 months and non-reach, respectively. Moreover, tumor burden beyond the up-to-11 criteria (HR: 2.95, 95% CI: 1.04-8.38) and a decrease in estimated glomerular filtration rate of more than 10% within 12 weeks (HR: 0.31, 0.11-0.88) were significantly related to PFS in the multi-variable analysis. No patient discontinued ramucirumab during the treatment on account of side effects. CONCLUSION: Ramucirumab was an effective treatment option with good AFP response for advanced HCC patients in real-world experience. Tumor burden beyond the up-to-11 criteria and a decrease in estimated glomerular filtration rate were independent predictive factors for progression-free survival.

Proteomic analysis identifies HMGA2 as a novel biomarker of overall survival in papillary renal cell carcinoma.

PURPOSE: Although papillary renal cell carcinoma (PRCC) has a relatively favorable prognosis, a small number of patients with lymph node or distant metastasis have a poor prognosis. Owing to the complex typing and heterogeneity of PRCC, it remains difficult to provide risk stratification. The objective of our research was to identify potential markers of PRCC prognosis. METHODS: We performed proteomics and bioinformatics analyses on six pairs of formalin-fixed paraffin-embedded tumor and paired normal tissue samples. The Cancer Genome Atlas (TCGA) data were used to analyze the prognostic value of differentially expressed proteins (DEPs) in PRCC. We verified the expression of the major biomarker through immunohistochemistry (IHC) in 91 PRCC tumor specimens. RESULTS: Proteomic analysis revealed 1544 DEPs between tumor and paired normal tissues. PRCC transcriptomic data from the TCGA database revealed that compared to non-tumor tissues, the expression of high-mobility group protein A2 (HMGA2) was upregulated in tumor tissues, and patients with high HMGA2 expression exhibited shorter overall survival times. HMGA2 was associated with PRCC tissue subtype and higher cell pleomorphism. Both TCGA and IHC results showed that HMGA2 expression was associated with lymph node metastasis and clinical stage. CONCLUSION: HMGA2 was positively correlated with malignant progression and could be a valuable novel prognostic biomarker for PRCC risk stratification.

Alternative Z-genome biosynthesis pathway shows evolutionary progression from Archaea to phage.

Many bacteriophages evade bacterial immune recognition by substituting adenine with 2,6-diaminopurine (Z) in their genomes. The Z-genome biosynthetic pathway involves PurZ that belongs to the PurA (adenylosuccinate synthetase) family and bears particular similarity to archaeal PurA. However, how the transition of PurA to PurZ occurred during evolution is not clear; recapturing this process may shed light on the origin of Z-containing phages. Here we describe the computer-guided identification and biochemical characterization of a naturally existing PurZ variant, PurZ0, which uses guanosine triphosphate as the phosphate donor rather than the ATP used by PurZ. The atomic resolution structure of PurZ0 reveals a guanine nucleotide binding pocket highly analogous to that of archaeal PurA. Phylogenetic analyses suggest PurZ0 as an intermediate during the evolution of archaeal PurA to phage PurZ. Maintaining the balance of different purines necessitates further evolvement of guanosine triphosphate-using PurZ0 to ATP-using PurZ in adaptation to Z-genome life.