Kuntai capsule for the treatment of diminished ovarian reserve: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Diminished ovarian reserve (DOR) results in reduced fertility. Kuntai capsule, a Chinese patent medicine, which can nourish the heart and kidneys, has shown promising efficacy in its treatment. However, there is no enough clinical evidence to confirm the efficacy and safety of Kuntai capsule. AIM OF THE STUDY: This review aims to evaluate Kuntai capsule's potential benefits and detriments for diminished ovarian reserve. MATERIALS AND METHODS: Databases namely China National Knowledge Infrastructure, WANFANG Database, Chinese Science and Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library, and Embase were searched from their inception to July 2023. We included randomized controlled trials (RCTs) comparing Kuntai capsule to hormone therapy (HT) and Kuntai capsule in combination with HT to HT alone for DOR treatment. The risk of bias was evaluated using RoB 1.0. A Meta-analysis was performed using RevMan 5.4 software. The primary outcomes were antral follicle count (AFC) and serum anti-Müllerian hormone (AMH), secondary outcomes were follicle-stimulating hormone (FSH) and adverse reactions. RESULTS: A Meta-analysis of 12 randomized controlled trials (RCTs), encompassing a total of 905 DOR patients was conducted. The results indicated that the combination of Kuntai capsule with HT exhibited superior efficacy in enhancing AFC (MD = 1.34, 95% CI [0.96,1.72]) and AMH levels (MD = 1.09 (ng/mL) 95% CI[0.80,1.38]), Kuntai capsule demonstrated improvements in AFC (MD = 0.65, 95% CI [0.48,0.83]) in DOR patients compared to HT alone. CONCLUSIONS: Based on the available results, the combination of Kuntai capsule with HT appears to improve the AFC, AMH and FSH levels of DOR patients. Kuntai capsule alone appears to improve the AFC and FSH levels of DOR patients. However, included trials had methodological quality issues, further standardized research is required.

Communities of Care Approach: Developing a Place-based Model of Care and Building Partnerships in the Communities in Central Singapore.

The population in Singapore is ageing, adding pressure to community care as the health and social needs of its residents increase. This has accelerated the pace at which Regional Health Systems adopt and deliver its population health strategies from early prevention, chronic disease management, crisis care to end-of-life care. To this end, the Central Health Integrated Care Network (ICN) began its journey to develop Communities of Care (CoCs) with other health and social care partners to meet the needs of residents in the Central Zone of Singapore. This paper describes the processes and steps taken by Central Health ICN to build partnerships with other agencies and organisations to build place-based models of care in the local neighbourhoods. The faciliating factors and the barriers faced in the implementation of CoCs were described to allow sharing of such learnings on large scale change. Strategies in overcoming some of the challenges were also presented to demonstrate the iterative processes required in building integrated place-based models of care to meet the needs of the residents in different communities.

Effects of Entry Grades on Students' Academic Performance Under Homogeneous Educational Resources.

Background: A minor difference in college entrance examination scores can result in vastly different educational resources in China, so it has been debated whether it is the difference in the student population or the difference in educational resources that causes the difference in medical graduates. We aimed to evaluate the effects of entry grades on students' academic performance under homogeneous educational resources. Methods: Students in grade 2016 with 13-point difference in the average admission scores of 2 medicine schools in Sun Yat-sen University were educated in mixed classes and were taught with the same educators during the 5 years of undergraduate period. The grades, graduation, and postgraduate enrollment rates of the students were compared between the two campuses. Results: The average admission scores for Shenzhen Campus (SZC) students are 13 points lower than those of Guangzhou North Campus (GZNC) (613 points vs 626 points). After 5 years of homogeneous education, comparing the GZNC students with the SZC students, there were no significant differences in the average total score (80.2 ± 4.6 vs 80.0 ± 5.6, P = 0.691), the average compulsory course (78.9 ± 3.4 vs 78.4 ± 6.1, P = 0.438), the average core course score (78.8 ± 7.4 vs 78.7 ± 5.0, P=0.860) and the average clerkship score (85.1 ± 7.2 vs 84.6 ± 2.7, P=0.275). However, the completion rate for SZC was higher than for GZNC (93.94% vs 86.27%, P=0.009). There was no statistical difference in postgraduate enrolment between the two institutions (P=0.758). Conclusion: Given the same educational resources, more medical students with lower entrance scores completed their studies and achieved the same percentage of postgraduate acceptance. This finding suggests that a key component of improving the quality of medical higher education in China may be to further rationalize the allocation of high-quality educational resources, rather than to pursuing students with high entrance examination scores.

1. Undergraduates from two medical schools with different average admission scores were educated with the same resources during the 5-year undergraduate period. After 5 years of homogeneous education, more students with lower entrance scores completed their studies and achieved the same percentage of postgraduate acceptance. 2. The key to improving educational quality is to optimize educational resources, not just to recruit high-scoring students.

ColorNetVis: An Interactive Color Network Analysis System for Exploring the Color Composition of Traditional Chinese Painting.

In the field of digital humanities, color research aims to discover explanations for painting history and color usage habits. However, researchers analyzing color relationships is challenging and time-consuming, as it requires color extraction and a detailed review of many painting images for reference and comparison of color relationships. In our work, we propose ColorNetVis, an interactive color network analysis tool that enables researchers to explore color relationships through color networks. The core of ColorNetVis is a bipartite network model that establishes a bipartite relationship between colors and Chinese painting within a scope based on color difference measurement. It constructs a one-mode color network through projection algorithms and similarity calculation methods to discover the relationship between colors. We propose a coordinated set of views to demonstrate the combination of determined color networks with painting types and real-world attributes. We use color space view, color attribute distribution view, and single color query components to assist researchers in conducting detailed color analysis and validation. Through case studies, researcher reviews, and user studies, we demonstrate that ColorNetVis can effectively help researchers discover knowledge of color relationships and potential color research directions.

26.5625 Gbaud PAM-4 short-reach transmission at 75°C using 850 nm VCSELs with strategic oxide guiding layer positioning.

This article presents an all-epitaxy approach to reduce the root mean square spectral width (ΔλR M S) of 850 nm oxide-confined vertical cavity surface-emitting lasers (VCSELs) with a large aperture of 7 µm through strategic optimization of the oxide guiding layer within the epitaxy structure. At 75°C, the VCSEL demonstrates a ΔλR M S of ∼0.3 nm at a bias current of 7.5 mA. Furthermore, the VCSEL achieves successful transmission of 26.5625 Gbaud PAM-4 modulation over a short-reach (SR) OM4 fiber link while maintaining a TDECQ budget below the 4.5 dB specified by 50G IEEE Ethernet standards.

The association between neonatal birthweight discordance and preeclampsia in twin pregnancy.

PURPOSE: To investigate the association between neonatal birthweight (NBW) discordance and preeclampsia (PE) in twin pregnancy. METHODS: This was a single-center retrospective cohort study. Women with two live births in the First Affiliated Hospital of Sun Yat-sen University from January 2011 to June 2020 were eligible. They were classified into four groups based on the quartiles of NBW discordance in monochorionic (MC) and dichorionic (DC) twin pregnancy. The relationship between NBW discordance and the risk of PE was assessed by logistic regression, subgroup analyses was further analyzed. RESULTS: A total of 1566 women were eligible for the final analysis, there were 445 MC cases and 1121 DC cases. No matter in monochorionic or dichorionic pregnancy, higher NBW discordance quartiles were associated with increased risks of PE. Compared with women in the lowest NBW discordance quartile, women in the highest NBW discordance quartile had approximately 3.6 and 6.0 times risk of PE in monochorionic and dichorionic pregnancy respectively. The association between quartiles of NBW discordance and the risk of PE were higher in dichorionic pregnancy than in monochorionic pregnancy. No matter in MC or DC pregnancy, no significant interaction effects were identified for maternal age, pregnancy body mass index, mode of conception and whether complicated with gestational diabetes mellitus. CONCLUSIONS: The increased NBW discordance quartile was related to an increased risk of PE. Assessing estimated fetal weight discordance by using ultrasound in clinical practice to predict PE remained to be further researched.

The 'Candidatus phytoplasma ziziphi' effectors SJP1 and SJP2 destabilise the bifunctional regulator ZjTCP7 to modulate floral transition and shoot branching.

Phytoplasmic SAP11 effectors alter host plant architecture and flowering time. However, the exact mechanisms have yet to be elucidated. Two SAP11-like effectors, SJP1 and SJP2, from 'Candidatus Phytoplasma ziziphi' induce shoot branching proliferation. Here, the transcription factor ZjTCP7 was identified as a central target of these two effectors to regulate floral transition and shoot branching. Ectopic expression of ZjTCP7 resulted in enhanced bolting and earlier flowering than did the control. Interaction and expression assays demonstrated that ZjTCP7 interacted with the ZjFT-ZjFD module, thereby enhancing the ability of these genes to directly bind to the ZjAP1 promoter. The effectors SJP1 and SJP2 unravelled the florigen activation complex by specifically destabilising ZjTCP7 and ZjFD to delay floral initiation. Moreover, the shoot branching of the ZjTCP7-SRDX transgenic Arabidopsis lines were comparable to those of the SJP1/2 lines, suggesting the involvement of ZjTCP7 in the regulation of shoot branching. ZjTCP7 interacted with the branching repressor ZjBRC1 to enhance suppression of the auxin efflux carrier ZjPIN3 expression. ZjTCP7 also directly bound to and upregulated the auxin biosynthesis gene ZjYUCCA2, thereby promoting auxin accumulation. Our findings confirm that ZjTCP7 serves as a bifunctional regulator destabilised by the effectors SJP1 and SJP2 to modulate plant development.

Immunoproteasomal Processing of IsoLG-Adducted Proteins Is Essential for Hypertension.

BACKGROUND: Hypertension is characterized by CD8+ T cell activation and infiltration into peripheral tissues. CD8+ T cell activation requires proteasomal processing of antigenic proteins. It has become clear that isoLG (isolevuglandin)-adduced peptides are antigenic in hypertension; however, IsoLGs inhibit the constitutive proteasome. We hypothesized that immunoproteasomal processing of isoLG-adducts is essential for CD8+ T cell activation and inflammation in hypertension. METHODS: IsoLG adduct processing was studied in murine dendritic cells (DCs), endothelial cells (ECs), and B8 fibroblasts. The role of the proteasome and the immunoproteasome in Ang II (angiotensin II)-induced hypertension was studied in C57BL/6 mice treated with bortezomib or the immunoproteasome inhibitor PR957 and by studying mice lacking 3 critical immunoproteasome subunits (triple knockout mouse). We also examined hypertension in mice lacking the critical immunoproteasome subunit LMP7 specifically in either DCs or ECs. RESULTS: We found that oxidant stress increases the presence of isoLG adducts within MHC-I (class I major histocompatibility complex), and immunoproteasome overexpression augments this. Pharmacological or genetic inhibition of the immunoproteasome attenuated hypertension and tissue inflammation. Conditional deletion of LMP7 in either DCs or ECs attenuated hypertension and vascular inflammation. Finally, we defined the role of the innate immune receptors stimulator of interferon genes and TLR7/8 (toll-like receptor 7/8) as drivers of LMP7 expression in ECs. CONCLUSIONS: These studies define a previously unknown role of the immunoproteasome in DCs and ECs in CD8+ T cell activation. The immunoproteasome in DCs and ECs is critical for isoLG-adduct presentation to CD8+ T cells, and in the endothelium, this guides homing and infiltration of T cells to specific tissues.

Adipose-derived stem cell modulate tolerogenic dendritic cell-induced T cell regulation is correlated with activation of Notch-NFκB signaling.

BACKGROUND: Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs. METHODS: Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs. RESULTS: Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway). CONCLUSIONS: ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application.

Complex association of body mass index and outcomes in patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy.

BACKGROUND AIMS: Chimeric antigen receptor-T (CAR-T) cells have exhibited remarkable efficacy in treating refractory or relapsed multiple myeloma (R/R MM). Although obesity has a favorable value in enhancing the response to immunotherapy, less is known about its predictive value regarding the efficacy and prognosis of CAR-T cell immunotherapy. METHODS: We conducted a retrospective study of 111 patients with R/R MM who underwent CAR-T cell treatment. Using the body mass index (BMI) classification, the patients were divided into a normal-weight group (73/111) and an overweight group (38/111). We investigated the effect of BMI on CAR-T cell therapy outcomes in patients with R/R MM. RESULTS: The objective remission rates after CAR-T cell infusion were 94.7% and 89.0% in the overweight and normal-weight groups, respectively. The duration of response and overall survival were not significant difference between BMI groups. Compared to normal-weight patients, overweight patients had an improved median progression-free survival. There was no significant difference in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome between the subgroups. In terms of hematological toxicity, the erythrocyte, hemoglobin, platelet, leukocyte and neutrophil recovery was accelerated in the overweight group. Fewer patients in the overweight group displayed moderate percent CD4 and CD4/CD8 ratios compared to the normal-weight group. Furthermore, the percent CD4 ratios were positively correlated with the levels of cytokines [interleukin-2 (IL-2) (day 14), interferon gamma (IFN-γ) (day 7) and tumor necrosis factor alpha (TNF-α) (days 14 and 21)] after cells infusion. On the other hand, BMI was positively associated with the levels of IFN-γ (day 7) and TNF-α (days 14 and 21) after CAR-T cells infusion. CONCLUSIONS: Overall, this study highlights the potential beneficial effect of a higher BMI on CAR-T cell therapy outcomes.

Comparison of efficacy and safety of PD-1/PD-L1 combination therapy in first-line treatment of advanced NSCLC: an updated systematic review and network meta-analysis.

BACKGROUND: The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens. METHODS: The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history. RESULTS: Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38-0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26-0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25-0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31-0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28-0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associated with the best PFS and OS benefits. CONCLUSION: For patients with advanced non-selective PD-L1 NSCLC, two effective regimens are Pen + CT and Niv + Bev + CT, which rank first in OS and PFS among all patients. Cam + CT and Tor + CT have advantages for OS in patients with SqNSCLC and Non-sqNSCLC, respectively. Niv + Ipi + CT provided the best OS benefit for patients with an ECOG score of 0, while Pem + CT may be the most effective treatment for patients with an ECOG score of 1. Pem + CT has a better effect on female patients and non-smokers. Sin + CT was found to be the most effective treatment for male patients and the smoking subgroup, while Cam + CT was found to be the most effective for PFS. In addition, Tor + CT was associated with the best PFS for patients with negative PD-L1 expression. Pem + CT was found to significantly improve both PFS and OS compared to CT alone. For patients with positive PD-L1 expression, Sin + CT and Cam + CT were found to be optimal for OS and PFS, respectively. It is important to note that, with the exception of Tor + CT, the toxicity of the other combinations was higher than that of CT alone.

The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-ß1-induced fibrotic responses in renal fibroblasts and epithelial cells independent of Smad3 phosphorylation. Cellular uptake of Cf48 and its pro-fibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3'-untranslated region of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis which operates as an RNA-binding peptide to promote the production of extracellular matrix.

Perceived HRM and turnover intentions of elderly care workers: perspective from person-job fit and institutional ownership.

BACKGROUND: Although the phenomenon of high turnover rate in the elderly care industry has existed for a long time, there are few studies that have constructed frameworks to comprehensively analyze the strength of the effects of various factors on the turnover intention of elderly care workers.. This study analyzed the impact of different types of perceived human resource management practices on elderly care workers' turnover intentions and whether this relationship is moderated by person-job fit and ownership of elderly care institutions. METHODS: This is a cross-sectional and regional survey study. The study included questionnaire survey data from a total of 305 elderly care workers from 42 elderly care institutions in 21 provinces in China during June to September 2021. Descriptive statistics, Pearson correlation coefficient, multiple regression, and heterogeneity analyses were performed. RESULTS: Perceived work environment ( ß =-0.5164, p< 0.01), perceived occupational protection ( ß =-0.3390, p< 0.01), perceived welfare benefits ( ß = -0.2620, p< 0.01) and perceived competency training ( ß = -0.1421, p< 0.1) were all significantly and negatively related to turnover intentions, the quality of perceived work environment has the greatest impact on elderly care workers' turnover intentions. Under the moderating effects of person-job fit and ownership of elderly care institutions, there existed heterogeneity between perceived human resource management and turnover intentions among elderly care workers. High level of person-job fit and elderly care institutions' public feature can effectively weaken the negative impact of each type of perceived human resource management on turnover intention among elderly care workers. CONCLUSIONS: The managers of elderly care institutions should optimize the management mechanism, typically pay attention to elderly care workers' working environment, formulate and improve the professional standards and job requirements for elderly care workers, promote the public welfare value of nursing care services, and strengthen the sense of honor and responsibility of elderly care workers to reduce the turnover rate.

ScrollTimes: Tracing the Provenance of Paintings as a Window into History.

The study of cultural artifact provenance, tracing ownership and preservation, holds significant importance in archaeology and art history. Modern technology has advanced this field, yet challenges persist, including recognizing evidence from diverse sources, integrating sociocultural context, and enhancing interactive automation for comprehensive provenance analysis. In collaboration with art historians, we examined the handscroll, a traditional Chinese painting form that provides a rich source of historical data and a unique opportunity to explore history through cultural artifacts. We present a three-tiered methodology encompassing artifact, contextual, and provenance levels, designed to create a "Biography" for handscroll. Our approach incorporates the application of image processing techniques and language models to extract, validate, and augment elements within handscroll using various cultural heritage databases. To facilitate efficient analysis of non-contiguous extracted elements, we have developed a distinctive layout. Additionally, we introduce ScrollTimes, a visual analysis system tailored to support the three-tiered analysis of handscroll, allowing art historians to interactively create biographies tailored to their interests. Validated through case studies and expert interviews, our approach offers a window into history, fostering a holistic understanding of handscroll provenance and historical significance.

Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

Electron Deficient Ir-O Bonds Promote Heterogeneous Ir-Catalyzed Anti-Markovnikov Hydroboration of Alkenes under Mild Neat Conditions.

Tuning electronic characteristics of metal-ligand bonds based on reaction pathways to achieve efficient catalytic processes has been widely studied and proven to be feasible in homogeneous catalysis, but it is scarcely investigated in heterogeneous catalysis. Herein, we demonstrate the regulation of the electronic configuration of Ir-O bonds in an Ir single-atom catalyst according to the borane activation mechanism. Ir-O bonds in Ir1/Ni(OH)x are found to be more electron-poor than those in Ir1/NiOx. Despite the mild solvent-free conditions and ambient temperature, Ir1/Ni(OH)x exhibits outstanding performance for the hydroboration of alkenes, furnishing the desired alkylboronic esters with a turnover frequency value of ≤3060 h-1 and 99% anti-Markovnikov selectivity, which is significantly better than that of Ir1/NiOx (42 h-1). It is further proven that the more electron-poor Ir-O bonds as active centers are more oxidative and so benefit the activation of the H-B bond in the reductive pinacolborane.

Modulation of gut microbiota and metabolites by Flammulina velutipes polysaccharides during in vitro human fecal fermentation: Unveiling Bacteroides as a potential primary degrader.

Flammulina velutipes, a widely cultivated species of edible fungus, exhibits diverse functional activities attributed to its polysaccharides. In this study, we employed an in vitro model to investigate the impact of F. velutipes polysaccharides (FVP) fermentation on gut microbiota, with a particular focus on Bacteroides. FVP fermentation resulted in the proliferation of microbiota associated with short-chain fatty acid (SCFA) metabolism and suppression of Escherichia-Shigella. Bacteroides emerged as potential primary degraders of FVP, with species-level analysis identifying the preference of B. thetaiotaomicron and B. intestinalis in FVP degradation. Metabolomics analysis revealed significant increases in hypoxanthine and 7-methyladenine contents, with histidine metabolism emerging as the most enriched pathway. B. nordii and B. xylanisolvens exhibited the most influence on amino acid and SCFA metabolism. Understanding the mechanisms by which gut microbiota metabolize FVP can provide valuable insights into the potential of FVP to promote intestinal health and disease prevention.

Jiawei Dachaihu decoction protects against mitochondrial dysfunction in atherosclerosis (AS) mice with chronic unpredictable mild stress (CUMS) via SIRT1/PGC-1α/TFAM/LON signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: JiaWei DaChaiHu is composed of Bupleurum chinense, Scutellaria baicalensis, Pinellia ternata, Paeonia lactiflora, Zingiber officinale Roscoe, Poncirus tuifoliata, Rheum palmatum L., Curcumae Radix, Herba Lysimachiae, Ziziphus. JiaWei DaChaiHu one of the most common traditional Chinese medicines for the treatment of depression. AIM OF THE STUDY: The chronic unpredictable mild stress (CUMS) has been shown to promote atherosclerosis (AS). Dachaihu has been widely used in traditional Chinese medicine and has been known to exert distinct pharmacological effects. This investigation aims to examine the therapeutic effect of Jiawei Dachaihu extract on AS animal models with CUMS. METHODS: AS-CUMS mice model was established by Apoe-/- mice. Mice were treated with Jiawei Dachaihu. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) levels were measured using ELISA kits. Aortic tissue pathologic changes detected by oil red O staining. Mice behavioral changes detected by sucrose preference test and sucrose preference test. The relative mRNA expression levels of CRH, ND1, and TFAM were determined by qRT-PCR. 5-HT1A, BDNF, LON, TFAM, PGC-1α, and SIRT1 protein expression determined by western blotting. ATP content detected by ATP kits. RESULTS: The treatment with Jiawei Dachaihu extract alleviated the veins plaque and reduced stress signs in vitro and in vivo. It increased the ATP and HDL-C levels while decreased the TC, TG, LDL-C levels. Jiawei Dachaihu extract treatment upregulated Lon, SIRT1, TFAM, PGC-1α, BDNF, and 5-HT1A protein expression and regained mitochondrial function. CONCLUSION: Jiawei Dachaihu extract could alleviate AS and reduce CUMS by upregulating the SIRT1/PGC-1α signaling and promoted its crosstalk with Lon protein to maintain mitochondrial stability.

CBC-1 as a Cynanbungeigenin C derivative inhibits the growth of colorectal cancer through targeting Hedgehog pathway component GLI 1.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers that results in death in worldwide. The Hedgehog (HH) signalling pathway regulates the initiation and progression of CRC. Inhibiting the HH pathway has been presented as a potential treatment strategy in recent years. Cynanbungeigenin C (CBC) is a new type of C21 steroid that has been previously reported for the treatment of medulloblastoma. However, its further investigation was limited by its poor water solubility. In this study, six new CBC derivatives were synthesized through the structural modification of CBC, and four of them showed better water solubility than CBC. Moreover, their antiproliferative activities on CRC were evaluated. It was found that CBC-1 presented the best inhibitory effect on three types of CRC cell lines, and this effect was superior to that of CBC. Mechanistically, CBC-1 inhibited the proliferation of CRC cells through regulation of mRNA and proteins of the HH pathway according to qRT-PCR and Western blotting analysis. Furthermore, Cellular Thermal Shift Assay results indicated that CBC-1 regulated this signalling pathway by targeting glioma­associated oncogene (GLI 1).In addition, cell apoptosis was induced increasingly by transfection with GLI 1 siRNA or treatment with CBC-1 to downregulate GLI 1. Last, the in vivo results demonstrated that CBC-1 significantly reduced tumour size and downregulated GLI 1 in CRC. Therefore, this study suggests that CBC-1, a new GLI 1 inhibitor derived from natural products, may be developed as a potential antitumour candidate for CRC treatment.

Dendritic polymer prodrug-based unimolecular micelles for pH-responsive co-delivery of doxorubicin and camptothecin with synergistic controlled drug release effect.

Combination chemotherapy has been recognized as a more powerful strategy for tumor treatment rather than the single chemotherapy. However, the interactive mechanism of the two hydrophobic chemotherapeutic drugs has not been explored by now. Aiming for a better synergistic effect, such interactive mechanism was investigated in the present work, by designing CPT@DOX-DPUTEA-PEG nanomedicine with encapsulated camptothecin (CPT) and conjugated doxorubicin (DOX). The synergistic controlled drug release effect was found for the two drugs loaded on the different sites of the dendritic polyurethane core. Synergism was achieved on the HepG2 cells with a combination index (CI) of 0.58 in the in vitro cellular experiments. The results demonstrated the promising application of the unimolecular micelles-based nanomedicine with independently loading of two hydrophobic chemotherapeutic drugs.