Development and validation of a nomogram to predict impacted ureteral stones via machine learning.

BACKGROUND: To develop and evaluate a nomogram for predicting impacted ureteral stones using some simple and easily available clinical features. METHODS: From June 2019 to July 2022, 480 patients who underwent ureteroscopic lithotripsy (URSL) for ureteral calculi were enrolled in the study. From the eligible study population between June 2019 and December 2020, a training and validation set was randomly generated in a 7:3 ratio. To further evaluate the generalization performance of the nomogram, we performed an additional validation using the data from January 2021 to July 2022. Lasso regression analysis was used to identify the most useful predictive features. Subsequently, a multivariate logistic regression algorithm was applied to select independent predictive features. The predictive performance of the nomogram was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves and decision Curve Analysis (DCA). The Hosmer-Lemeshow Test was utilized to evaluate the overall goodness of fit of the nomogram. RESULTS: Multivariate logistic regression analysis showed that flank pain, hydronephrosis, stone length/width, HU below (Hounsfield unit density of the ureter center below the stone), HU above/below (HU above divided by HU below) and UWT (ureteral wall thickness) were ascertained as independent predictors of impacted ureteral stones. The nomogram showed outstanding performance within the training dataset, with the area under the curve (AUC) of 0.907. Moreover, the AUC was 0.874 in the validation dataset. The ROC curve, calibration curve, DCA curve and Hosmer-Lemeshow Test suggested that the nomogram maintains excellent clinical applicability and demonstrates commendable performance. Similar results were achieved in the test dataset as well. CONCLUSIONS: We established a nomogram that can be effectively used for preoperative diagnosis of impacted ureteral stones, which is of great significance for the treatment of this disease.

The compositional and functional imbalance of the gut microbiota in CKD linked to disease patterns.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is on the rise, posing a significant public health challenge. Although gut microbiome dysbiosis has been implicated in the impairment of kidney functions, the existence of pathological subtypes-linked differences remains largely unknown. We aimed to characterize the intestinal microbiota in patients with membranous nephropathy (MN), IgA nephropathy (IgAN), minimal change disease (MCD), and ischemic renal injury (IRI) in order to investigate the intricate relationship between intestinal microbiota and CKD across different subtypes. METHODS: We conducted a cross-sectional study involving 94 patients with various pathological patterns of CKD and 54 healthy controls (HCs). The clinical parameters were collected, and stool samples were obtained from each participant. Gut microbial features were analyzed using 16S rRNA sequencing and taxon annotation to compare the HC, CKD, MN, IgAN, MCD, and IRI groups. RESULTS: The CKD subjects exhibited significantly reduced alpha diversity, modified community structures, and disrupted microbial composition and potential functions compared to the control group. The opportunistic pathogen Klebsiella exhibited a significant enrichment in patients with CKD, whereas Akkermansia showed higher abundance in HCs. The study further revealed the presence of heterogeneity in intestinal microbial signatures across diverse CKD pathological types, including MN, IgAN, MCD, and IRI. The depression of the family Lachnospiraceae and the genus Bilophila was prominently observed exclusively in patients with MN, while suppressed Streptococcus was detected only in individuals with MCD, and a remarkable expansion of the genus Escherichia was uniquely found in cases of IRI. The study also encompassed the development of classifiers employing gut microbial diagnostic markers to accurately discriminate between distinct subtypes of CKD. CONCLUSIONS: The dysregulation of gut microbiome was strongly correlated with CKD, exhibiting further specificity towards distinct pathological patterns. Our study emphasizes the significance of considering disease subtypes when assessing the impact of intestinal microbiota on the development, diagnosis, and treatment of CKD.

Volume replacement in tumor plastic surgery and breast-conserving surgery using 3D grid and strip­shaped acellular dermal matrix: Two case reports.

The present study was driven by the scarcity of suitable materials for mending partial breast defects and the imperative considerations of safety and durability. The current study presents findings from two female patients, aged 59 and 40, who underwent breast cancer treatment. Patient 1 underwent a mastectomy with a sentinel lymph node biopsy, while patient 2 underwent a partial mastectomy with axillary lymph node dissection. Core needle biopsy confirmed invasive ductal carcinoma in both cases. Breast ultrasound revealed hypoechoic lesions with smooth edges. The reconstruction of the breast defect employed an acellular dermal matrix, and the safety and cosmetic outcomes for each patient were analyzed. At 3 months post-radiotherapy, neither patient experienced significant complications. The preservation of breast contour and volume was satisfactory, with no postoperative tumor recurrences detected. In summary, utilizing an acellular dermal matrix with a three-dimensional grid design for partial breast defect reconstruction offers a viable alternative that aligns with oncological safety standards and provides good cosmetic results.

Advancing Anode Performance in Aqueous Zinc-Ion Batteries: A Review of Metal-Organic Framework-Based Strategies.

Aqueous zinc-ion batteries (AZIBs) are garnering substantial research interest in electric vehicles, energy storage systems, and portable electronics, primarily for the reason that the inexpensive cost, high theoretical specific capacity, and environmental sustainability of zinc metal anodes, which are an essential component to their design. Nonetheless, the progress of AZIBs is hindered by significant obstacles, such as the occurrence of anodic side reactions (SR) and the formation of zinc dendrites. Metal-organic framework (MOF)-based materials are being explored as promising alternatives owing to homogeneous porous structure and large specific surface areas. There has been a rare overview and discussion on strategies for protecting anodes using MOF-based materials. This review specifically aims to investigate cutting-edge strategies for the design of highly stable MOF-based anodes in AZIBs. Firstly, the mechanisms of dendrites and SR are summarized. Secondly, the recent advances in MOF-based anodic protection including those of pristine MOFs, MOF composites, and MOF derivatives are reviewed. Furthermore, the strategies involving MOF-based materials for zinc anode stabilization are presented, including the engineering of surface coatings, three-dimensional zinc structures, artificial solid electrolyte interfaces, separators, and electrolytes. Finally, the ongoing challenges and prospective directions for further enhancement of MOF-based anodic protection technologies in AZIBs are highlighted.

Exploring the Impact of Workplace Violence on the Mental Health of Chinese Correctional Officers: A JD-R Model Approach.

Background: Correctional officers face widespread workplace violence and the resulting overwork that can profoundly damage their physical and mental health. Purpose: This study aims to investigate the mediating role of overwork in the relationship between workplace violence and the manifestation of physical and mental health issues among correctional officers. Methods: This study enlisted 472 eligible participants. Cross-sectional data were obtained using the Chinese version of the Workplace Violence Scale (WVS), while the physical and mental health of correctional officers was evaluated through relevant scales. Analysis involved descriptive statistics, correlation analyses, and tests for mediation models. Results: The study found significant correlations between workplace violence, overwork, and various mental health variables (depression, anxiety, stress, suicidal ideation, and insomnia), with correlations ranging from 0.135 to 0.822 (p < 0.01). Mediation analysis revealed that workplace violence directly impacts correctional officers' physical and mental health (p < 0.001) and also has an indirect effect through overwork (p < 0.023). These findings underscore the substantial impact of workplace violence on the health of correctional officers, both directly and indirectly. Conclusion: Workplace violence and overwork significantly contribute to the physical and mental health challenges faced by correctional officers. Overwork acts as a mediator in the relationship between workplace violence and these health issues. The study suggests addressing workplace violence and mental health issues among correctional officers by increasing their numbers, improving the work environment, and implementing enhanced welfare policies.

Intestinal microbiota by angiotensin receptor blocker therapy exerts protective effects against hypertensive damages.

Dysbiosis of the gut microbiota has been implicated in hypertension, and drug-host-microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)-shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB-modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well-controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB-modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post-FMT, especially with a decreased abundance of Lactobacillus, Aggregatibacter, and Desulfovibrio. Moreover, ARB-treated microbes contributed to increased intestinal Ciart, Per1, Per2, Per3, and Cipc gene levels and decreased Nfil3 and Arntl expression were detected in response to ARB-treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB-FMT rats, including 6beta-Hydroxytestosterone and Thromboxane B2. In conclusion, ARB-modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross-talk between antihypertensive medicines and the gut microbiome.

Research progress on m6A demethylase FTO and its role in gynecological tumors.

Recent advances in genomic research have increasingly focused on the fat mass- and obesity-associated (FTO) gene due to its notable correlation with obesity. Initially explored for its contribution to increased body weight, FTO was later discovered to function as an m6A demethylase. This pivotal role enhances our understanding of its broader implications across various pathologies. Epigenetic modifications, such as m6A, have been implicated in gynecological cancers, including ovarian, endometrial, and cervical malignancies. However, the precise mechanisms by which FTO influences the development of gynecological cancers remain largely unknown. This analysis underscores the growing relevance of investigations into the FTO gene in elucidating the mechanisms underlying gynecological cancers and exploring potential therapeutic avenues.

The costs, health and economic impact of air pollution control strategies: a systematic review.

BACKGROUND: Air pollution poses a significant threat to global public health. While broad mitigation policies exist, an understanding of the economic consequences, both in terms of health benefits and mitigation costs, remains lacking. This study systematically reviewed the existing economic implications of air pollution control strategies worldwide. METHODS: A predefined search strategy, without limitations on region or study design, was employed to search the PubMed, Scopus, Cochrane Library, Embase, Web of Science, and CEA registry databases for studies from their inception to November 2023 using keywords such as "cost-benefit analyses", "air pollution", and "particulate matter". Focus was placed on studies that specifically considered the health benefits of air pollution control strategies. The evidence was summarized by pollution control strategy and reported using principle economic evaluation measurements such as net benefits and benefit-cost ratios. RESULTS: The search yielded 104 studies that met the inclusion criteria. A total of 75, 21, and 8 studies assessed the costs and benefits of outdoor, indoor, and mixed control strategies, respectively, of which 54, 15, and 3 reported that the benefits of the control strategy exceeded the mitigation costs. Source reduction (n = 42) and end-of-pipe treatments (n = 15) were the most commonly employed pollution control methodologies. The association between particulate matter (PM) and mortality was the most widely assessed exposure-effect relationship and had the largest health gains (n = 42). A total of 32 studies employed a broader benefits framework, examining the impacts of air pollution control strategies on the environment, ecology, and society. Of these, 31 studies reported partially or entirely positive economic evidence. However, despite overwhelming evidence in support of these strategies, the studies also highlighted some policy flaws concerning equity, optimization, and uncertainty characterization. CONCLUSIONS: Nearly 70% of the reviewed studies reported that the economic benefits of implementing air pollution control strategies outweighed the relative costs. This was primarily due to the improved mortality and morbidity rates associated with lowering PM levels. In addition to health benefits, air pollution control strategies were also associated with other environmental and social benefits, strengthening the economic case for implementation. However, future air pollution control strategy designs will need to address some of the existing policy limitations.

Pattern and extent of intrahepatic infiltration of perihilar cholangiocarcinoma - A case-control study based on liver panoramic digital pathology.

BACKGROUND: The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research. MATERIALS AND METHODS: This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10 × 10 cm was used to panoramically assess the intrahepatic infiltration extent of PHCC. RESULTS: The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15,000 µm, 62.9% of PHCCs had DIHI greater than 1 cm away from the main tumor in liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI (P＜0.0001, P=0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100, 100%, and 69% respectively. CONCLUSION: The presence of DIHI in most PHCCs was a significant predictor of poor postoperative recurrence and survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment.

Long-term outcomes following hepatectomy in patients with lean non-alcoholic fatty liver disease-associated hepatocellular carcinoma versus overweight and obese counterparts: A multicenter analysis.

BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) as a significant etiology for hepatocellular carcinoma (HCC), lean NAFLD-HCC has emerged as a specific distinct subtype. This study sought to investigate long-term outcomes following curative-intent hepatectomy for early-stage NAFLD-HCC among lean patients compared with overweight and obese individuals. METHODS: A multicenter retrospective analysis was used to assess early-stage NAFLD-HCC patients undergoing curative-intent hepatectomy between 2009 and 2022. Patients were stratified by preoperative body mass index (BMI) into the lean (<23.0 kg/m2), overweight (23.0-27.4 kg/m2) and obese (≥27.5 kg/m2) groups. Study endpoints were overall survival (OS) and recurrence-free survival (RFS), which were compared among groups. RESULTS: Among 309 patients with NAFLD-HCC, 66 (21.3 %), 176 (57.0 %), and 67 (21.7 %) were lean, overweight, and obese, respectively. The three groups were similar relative to most liver, tumor, and surgery-related variables. Compared with overweight patients (71.3 % and 55.6 %), the lean individuals had a worse 5-year OS and RFS (55.4 % and 35.1 %, P = 0.017 and 0.002, respectively), which were comparable to obese patients (48.5 % and 38.2 %, P = 0.939 and 0.442, respectively). After adjustment for confounding factors, multivariable Cox-regression analysis identified that lean bodyweight was independently associated with decreased OS (hazard ratio: 1.69; 95 % confidence interval: 1.06-2.71; P = 0.029) and RFS (hazard ratio: 1.72; 95 % confidence interval: 1.17-2.52; P = 0.006) following curative-intent hepatectomy for early-stage NAFLD-HCC. CONCLUSIONS: Compared with overweight patients, individuals with lean NAFLD-HCC had inferior long-term oncological survival after hepatectomy for early-stage NAFLD-HCC. These data highlight the need for examination of the distinct carcinogenic pathways of lean NAFLD-HCC and its potential consequences in HCC recurrence.

Removal of mixed pollutants of perfluorooctanoic acid and 2,4,6-trichlorophenol via adsorption-photocatalysis using Ga2O3-Bi4O7 combining with fluorine-doped covalent triazine framework: Role of different active species.

Perfluorooctanoic acid (PFOA) and 2,4,6-trichlorophenol (2,4,6-TCP) are significant pollutants found in textile wastewater, posing severe threats to ecological environments. The construction of an adsorption-photocatalytic system enables the efficient removal of mixed pollutants by harnessing their synergistic effect, thereby overcoming the limitations of removing mixed pollutants with single water treatment technologies. Herein, fluorine-doped covalent triazine framework (F-CTF) was combined with Ga2O3-Bi4O7 heterojunction to obtain Ga2O3-Bi4O7/F-CTF (GaBi/CTF). F-CTF greatly facilitates the adsorption process and provides convenience for photocatalysis. Simultaneously, the excellent conductivity of F-CTF promoted the separation of photoinduced charge carriers in Ga2O3-Bi4O7. GaBi/CTF5 (5 is the mass percentage of F-CTF) showed excellent degradation performance, and the removal rates of PFOA and 2,4,6-TCP reached 93.0 % and 100.0 % within 90 min, respectively. Mechanistic analysis revealed that 2,4,6-TCP and PFOA were attacked by distinct active species because of the disparate characteristics. The presence of phenolic hydroxyl groups makes 2,4,6-TCP more vulnerable to superoxide radicals (·O2-) and hydroxyl radicals (·OH), whereas PFOA is oxidized by holes (h+). The coexistence of mixed pollutants with diverse characteristics enables optimal utilization of active species generated within photocatalytic system. Moreover, the good stability of GaBi/CTF5 provides a feasible solution for efficient treatment of mixed pollutants in textile wastewater.

Exercise-Induced Oxygen Desaturation Increases Arterial Stiffness in Patients with COPD During the 6WMT.

Objective: Given the established impact of exercise in reducing arterial stiffness and the potential for intermittent hypoxia to induce its elevation, this study aims to understand how oxygen desaturation during exercise affects arterial stiffness in individuals with COPD. Methods: We enrolled patients with stable COPD from China-Japan Friendship Hospital from November 2022 to June 2023. The 6-minute walk test (6-MWT) was performed with continuous blood oxygen saturation (SpO2) monitoring in these patients. The patients were classified into three groups: non-exercise induced desaturation (EID), mild-EID and severe-EID, according to the changes in SpO2 during the 6-MWT. The Cardio-Ankle Vascular Index (CAVI) and the change in CAVI (ΔCAVI, calculated as CAVI before 6MWT minus CAVI after the 6MWT) were measured before and immediately after the 6MWT to assess the acute effects of exercise on arterial stiffness. GOLD Stage, pulmonary function, and other functional outcomes were also measured in this study. Results: A total of 37 patients with stable COPD underwent evaluation for changes in CAVI (ΔCAVI) before and after the 6-MWT. Stratification based on revealed three subgroups: non-EID (n=12), mild-EID (n=15), and severe-EID (n=10). The ΔCAVI values was -0.53 (-0.95 to -0.31) in non-EID group, -0.20 (-1.45 to 0.50) in mild-EID group, 0.6 (0.08 to 0.73) in severe-EID group. Parametric tests indicated significant differences in ΔCAVI among EID groups (p = 0.005). Pairwise comparisons demonstrated significant distinctions between mild-EID and severe-EID groups, as well as between non-EID and severe-EID groups (p = 0.048 and p = 0.003, respectively). Multivariable analysis, adjusting for age, sex, GOLD stage, diffusion capacity, and blood pressure, identified severe-EID as an independent factor associated with ΔCAVI (B = 1.118, p = 0.038). Conclusion: Patients with COPD and severe-EID may experience worsening arterial stiffness even during short periods of exercise.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain. In past work, we discovered that euchromatic histone lysine N-methyltransferase-2 (EHMT2/G9a) inhibitors were capable of un-silencing PWS-associated genes by restoring their expression from the maternal chromosome. Here, in mice lacking the Ehmt2 gene, we document un-silencing of the imprinted Snrpn/Snhg14 gene on the maternal chromosome in the late embryonic and postnatal brain. Using PWS and Angelman syndrome patient derived cells with either paternal or maternal deletion of 15q11-q13, we have found that chromatin of maternal PWS-IC is closed and has compact 3D folding confirmation. We further show that a new and distinct noncoding RNA preferentially transcribed from upstream of the PWS-IC interacts with EHMT2 and forms a heterochromatin complex to silence gene expression of SNRPN in CIS on maternal chromosome. Taken together, these findings demonstrate that allele-specific recruitment of EHMT2 is required to maintain the maternal imprints. Our findings provide novel mechanistic insights and support a new model for imprinting maintenance of the PWS imprinted domain.

Design and synthesis of 6,20-epoxy A-ring modified oridonin derivatives with antitumor activity through extrinsic and mitochondrial pathways.

Oridonin is an antitumor ent-kaurane diterpenoid that medicinal chemists have been paying close attention to in recent years. Herein, a novel 6,20-epoxy A-ring modified oridonin derivative 2 was obtained by a 6-step synthesis. A series of 14-O derivatives of 2 (EpskA1-EpskA24) were synthesized to further enhance the activity. Based on their cytotoxicity against MCF-7, A549 and L-02 cells, EpskA9, EpskA10 and EpskA21 were chosen for further screening to obtain a wider antitumor spectrum. Collectively, EpskA21 showed the most potent antiproliferative activity, inhibiting proliferation and migration, and inducing apoptosis and cell cycle arrest in MCF-7 and MIA-PaCa-2 cells. With the help of network pharmacology analysis, apoptosis-related proteins were selected and further tested by western blot assay. The inhibition of PI3K/AKT and an increase in the levels of Bax/Bcl-2 ratio, Cyt-C, cleaved-Caspase-9, cleaved-Caspase-3 and cleaved-PARP was observed, indicating that EpskA21 induced apoptosis through the mitochondrial pathway. Given that an increase in DR5 expression and activated Caspase-8 were also observed, the extrinsic apoptosis pathway might also be related to the antitumor effect.

Maize lipid droplet-associated protein 2 is recruited by a virus to enhance viral multiplication and infection through regulating cellular fatty acid metabolism.

Pathogen infection induces massive reprogramming of host primary metabolism. Lipid and fatty acid (FA) metabolism is generally disrupted by pathogens and co-opted for their proliferation. Lipid droplets (LDs) that play important roles in regulating cellular lipid metabolism are utilized by a variety of pathogens in mammalian cells. However, the function of LDs during pathogenic infection in plants remains unknown. We show here that infection by rice black streaked dwarf virus (RBSDV) affects the lipid metabolism of maize, which causes elevated accumulation of C18 polyunsaturated fatty acids (PUFAs) leading to viral proliferation and symptom development. The overexpression of one of the two novel LD-associated proteins (LDAPs) of maize (ZmLDAP1 and ZmLDAP2) induces LD clustering. The core capsid protein P8 of RBSDV interacts with ZmLDAP2 and prevents its degradation through the ubiquitin-proteasome system mediated by a UBX domain-containing protein, PUX10. In addition, silencing of ZmLDAP2 downregulates the expression of FA desaturase genes in maize, leading to a decrease in C18 PUFAs levels and suppression of RBSDV accumulation. Our findings reveal that plant virus may recruit LDAP to regulate cellular FA metabolism to promote viral multiplication and infection. These results expand the knowledge of LD functions and viral infection mechanisms in plants.

Stratifying risk of failure to achieve textbook outcomes among patients undergoing hepatectomy for hepatocellular carcinoma: A multicenter score validation study.

BACKGROUND AND AIMS: The concept of textbook outcomes (TOs) has gained increased attention as a critical metric to assess the quality and success of outcomes following complex surgery. A simple yet effective scoring system was developed and validated to predict risk of not achieving textbook outcomes (non-TOs) following hepatectomy for hepatocellular carcinoma (HCC). METHODS: Using a multicenter prospectively collected database, risk factors associated with non-TO among patients who underwent hepatectomy for HCC were identified. A predictive scoring system based on factors identified from multivariate regression analysis was used to risk stratify patients relative to non-TO. The score was developed using 70 % of the overall cohort and validated in the remaining 30 %. RESULTS: Among 3681 patients, 1458 (39.6 %) failied to experience a TO. Based on the derivation cohort, obesity, American Society of Anaesthesiologists score(ASA score), Child-Pugh grade, tumor size, and extent of hepatectomy were identified as independent predictors of non-TO. The scoring system ranged from 0 to 10 points. Patients were categorized into low (0-3 points), intermediate (4-6 points), and high risk (7-10 points) of non-TO. In the validation cohort, the predicted risk of developing non-TOs was 39.0 %, which closely matched the observed risk of 39.9 %. There were no differences among the predicted and observed risks within the different risk categories. CONCLUSIONS: A novel scoring system was able to predict risk of non-TO accurately following hepatectomy for HCC. The score may enable early identification of individuals at risk of adverse outcomes and inform surgical decision-making, and quality improvement initiatives.

Mechanochemical Synthesis of α-halo Alkylboronic Esters.

α-halo alkylboronic esters, acting as ambiphilic synthons, play a pivotal role as versatile intermediates in fields like pharmaceutical science and organic chemistry. The sequential transformation of carbon-boron and carbon-halogen bonds into a broad range of carbon-X bonds allows for programmable bond formation, facilitating the incorporation of multiple substituents at a single position and streamlining the synthesis of complex molecules. Nevertheless, the synthetic potential of these compounds is constrained by limited reaction patterns. Additionally, the conventional methods often necessitate the use of bulk toxic solvents, exhibit sensitivity to air/moisture, rely on expensive metal catalysts, and involve extended reaction times. In this report, a ball milling technique is introduced that overcomes these limitations, enabling the external catalyst-free multicomponent coupling of aryl diazonium salts, alkenes, and simple metal halides. This approach offers a general and straightforward method for obtaining a diverse array of α-halo alkylboronic esters, thereby paving the way for the extensive utilization of these synthons in the synthesis of fine chemicals.

2,2',4,4'-Tetrabromodiphenyl ether exposure disrupts blood-testis barrier integrity through CMA-mediated ferroptosis.

2,2',4,4'-Tetrabromodiphenyl ether (PBDE-47), being the most prevalent congener of polybrominated diphenyl ethers (PBDEs), has been found to accumulate greatly in the environment and induce spermatogenesis dysfunction. However, the specific underlying factors and mechanisms have not been elucidated. Herein, male Sprague-Dawley (SD) rats were exposed to corn oil, 10 mg/kg body weight (bw) PBDE-47 or 20 mg/kg bw PBDE-47 by gavage for 30 days. PBDE-47 exposure led to blood-testis barrier (BTB) integrity disruption and aberrant spermatogenesis. Given that Sertoli cells are the main toxicant target, to explore the potential mechanism involved, we performed RNA sequencing (RNA-seq) in Sertoli cells, and the differentially expressed genes were shown to be enriched in ferroptosis and lysosomal pathways. We subsequently demonstrated that ferroptosis was obviously increased in testes and Sertoli cells upon exposure to PBDE-47, and the junctional function of Sertoli cells was restored after treatment with the ferroptosis inhibitor ferrostatin-1. Since glutathione peroxidase 4 (GPX4) was dramatically reduced in PBDE-47-exposed testes and Sertoli cells and considering the RNA-sequencing results, we examined the activity of chaperone-mediated autophagy (CMA) and verified that the expression of LAMP2a and HSC70 was upregulated significantly after PBDE-47 exposure. Notably, Lamp2a knockdown not only inhibited ferroptosis by suppressing GPX4 degradation but also restored the impaired junctional function induced by PBDE-47. These collective findings strongly indicate that PBDE-47 induces Sertoli cell ferroptosis through CMA-mediated GPX4 degradation, resulting in decreased BTB-associated protein expression and eventually leading to BTB integrity disruption and spermatogenesis dysfunction.

A multimetallic nanozyme enhanced colorimetric biosensor for Salmonella detection on finger-actuated microfluidic chip.

Salmonella screening is essential to avoid food poisoning. A simple, fast and sensitive colorimetric biosensor was elaborately developed for Salmonella detection on a microfluidic chip through limiting air chambers for precise air control, switching rotary valves for accurate fluid selection, a convergence-and-divergence passive micromixer and an extrusion-and-suction active micromixer for efficient fluid mixing, and immune gold@platinum palladium nanocatalysts for effective signal amplification. The mixture of bacteria, immune magnetic nanobeads and nanocatalysts was first rapidly mixed to form nanobead-bacteria-nanocatalyst conjugates and magnetically separated for enrichment. After washing with water, the conjugates were used to catalyze colorless substrate and blue product was finally analyzed using ImageJ for quantifying bacterial concentration. The finger-actuated microfluidic chip enabled designated control of designated fluids in designated places towards designated directions by simple press-release operations on designated air chambers without any external power. Under optimal conditions, this sensor could detect Salmonella at 45 CFU/mL in 25 min.