The Barthel Index predicts surgical textbook outcomes following hepatectomy for elderly patients with hepatocellular carcinoma: A multicenter cohort study.

BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â€‹%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â€‹%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â€‹% vs. 72.1 â€‹%, P â€‹< â€‹0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â€‹% confidence interval 1.879-6.198, P â€‹< â€‹0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.

Regioselective and Enantioselective Nickel-Catalyzed Intermolecular Reductive Coupling of Aliphatic Alkenes with Imines.

Unactivated aliphatic alkenes are particularly desirable as starting materials because they are readily accessible in large quantities, but the enantioselective intermolecular reductive coupling of unactivated alkenes with imines is challenging. In this paper, we report a method for nickel-catalyzed intermolecular reductive coupling reactions between aliphatic alkenes and imines to yield chiral amines with excellent enantioselectivities and good linear selectivities. The reaction conditions are compatible with a broad range of aliphatic alkenes, including those derived from bioactive molecules. The success of this method can be attributed to the use of newly developed monodentate chiral spiro phosphine ligands.

Analysis of similarities and differences between transient symptomatic zinc deficiency and acrodermatitis enteropathica in children: a case report of a Chinese Yi-ethnic infant.

BACKGROUND: Transient symptomatic zinc deficiency (TSZD), an acquired type of zinc deficiency, is a rare, but probably underrecognized disease, extremely in breastfed premature with low birthweight infants. Its clinical manefestations are similar to Acrodermatitis enteropathica (AE), which is a genetic zinc absorption disorder caused by SLC39A4 gene mutations. This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. TSZD is often misdiagnosed as AE because of their extremely similar manefestations, characterized by a typical rash. Therefore, the differention between them is still a clinical challenging. CASE PRESENTATION: Here, we present a case of TSZD in a 4 month and 23 days female Chinese Yi-ethnic premature with AE-like skin lesions, mainly presenting periorificial, perianal and perineal crusted, eroded, erythemato-squamous eruption. Laboratory examination showed the patient's blood zinc level was significantly decreased. Further sequencing of the SLC39A4 gene showed no mutation in the infant and her parents. Skin lesions significantly improved after 6 days of initial zinc supplementation (3 mg/kg/d), and maintenance treatment with 1 mg/kg/day of zinc was discontinued after 8 months without recurrence. CONCLUSIONS: The clinical manifestations of TSZD and AE are extremely similar, leading to a high rate of clinical misdiagnosis. While genetic analysis of the SLC39A4 gene is a reliable method for differentiating TSZD from AE. It is recommended that SLC39A4 gene test should be performed as far as possible in children with AE-like rash.

Development and validation of nomograms to predict survival and recurrence after hepatectomy for intermediate/advanced (BCLC stage B/C) hepatocellular carcinoma.

BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.

Improving anaerobic digestion performance after severe acidification: Unveiling the impacts of Fe3O4-bentonite composites in co-digestion of waste activated sludge and food waste.

Acidification recovery in anaerobic digestion of food waste is challenging. This study explored its in-situ recovery using a co-substrate of food waste and waste activated sludge. Fe3O4 and bentonite were used as conductor and carrier, respectively, to enhance AD performance under severe acidification. The application of Fe3O4-bentonite resulted in a 152% increase in cumulative methane in the Fe3O4-bentonite 10 digester, demonstrating its effectiveness in restoring the acidified AD system. In acidified systems, bentonite enhanced the diversity and richness of microbial communities due to its buffering capacity. The excessive non-conductive polysaccharides excreted by bacteria in extracellular polymeric substances reduced the possibility of electron transfer by Fe3O4. However, in the synergistic application of Fe3O4 and bentonite, this resistance was alleviated, increasing the possibility of direct interspecies electron transfer, and accelerating the consumption of volatile fatty acids. This approach of integrating carrier and conductive materials is significant for in-situ restoration of acidified systems.

Conversion therapy for advanced hepatocellular carcinoma in the era of precision medicine: Current status, challenges and opportunities.

Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced-stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post-surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced-stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field.

Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation. It also plays a therapeutic role in restoring the intestinal mucosal barrier through the homing effect, regulation of the intestinal microbiome, and repair of intestinal epithelial cells. In the latest clinical trials, the safety and efficacy of MSCs in the treatment of IBD have been confirmed by transfusion of autologous or allogeneic bone marrow, umbilical cord, and adipose MSCs, as well as their derived extracellular vesicles. However, regarding the stable and effective clinical use of MSCs, several concerns emerge, including the cell sources, clinical management (dose, route and frequency of administration, and pretreatment of MSCs) and adverse reactions. This article comprehensively summarizes the effects and mechanisms of MSCs in the treatment of IBD and its advantages over conventional drugs, as well as the latest clinical trial progress of MSCs in the treatment of IBD. The current challenges and future directions are also discussed. This review would add knowledge into the understanding of IBD treatment by applying MSCs.

A reference-grade genome of the xerophyte Ammopiptanthus mongolicus sheds light on its evolution history in legumes and drought-tolerance mechanisms.

Plants that grow in extreme environments represent unique sources of stress-resistance genes and mechanisms. Ammopiptanthus mongolicus (Leguminosae) is a xerophytic evergreen broadleaf shrub native to semi-arid and desert regions; however, its drought-tolerance mechanisms remain poorly understood. Here, we report the assembly of a reference-grade genome for A. mongolicus, describe its evolutionary history within the legume family, and examine its drought-tolerance mechanisms. The assembled genome is 843.07 Mb in length, with 98.7% of the sequences successfully anchored to the nine chromosomes of A. mongolicus. The genome is predicted to contain 47 611 protein-coding genes, and 70.71% of the genome is composed of repetitive sequences; these are dominated by transposable elements, particularly long-terminal-repeat retrotransposons. Evolutionary analyses revealed two whole-genome duplication (WGD) events at 130 and 58 million years ago (mya) that are shared by the genus Ammopiptanthus and other legumes, but no species-specific WGDs were found within this genus. Ancestral genome reconstruction revealed that the A. mongolicus genome has undergone fewer rearrangements than other genomes in the legume family, confirming its status as a "relict plant". Transcriptomic analyses demonstrated that genes involved in cuticular wax biosynthesis and transport are highly expressed, both under normal conditions and in response to polyethylene glycol-induced dehydration. Significant induction of genes related to ethylene biosynthesis and signaling was also observed in leaves under dehydration stress, suggesting that enhanced ethylene response and formation of thick waxy cuticles are two major mechanisms of drought tolerance in A. mongolicus. Ectopic expression of AmERF2, an ethylene response factor unique to A. mongolicus, can markedly increase the drought tolerance of transgenic Arabidopsis thaliana plants, demonstrating the potential for application of A. mongolicus genes in crop improvement.

Corrigendum: Genomic evolution of BA.5.2 and BF.7.14 derived lineages causing SARS-CoV-2 outbreak at the end of 2022 in China.

[This corrects the article DOI: 10.3389/fpubh.2023.1273745.].

The influence of hot isostatic pressing on precipitates, mechanical properties of Mg-12Gd-0.8Zn-0.4Zr (wt.%) alloy manufactured by sand casting.

Microstructures and mechanical properties of Mg-12Gd-0.8Zn-0.4Zr (GZ1208K, wt.%) alloy under different treatments (as-cast: signed as nonHIP-GZ1208K, hot isostatic pressing (HIP): signed as HIP-GZ1208K) were characterized. Based on microstructure characterization, two prismatic precipitates, ß' and ß1 precipitates, and one basal precipitate, γ' precipitate, formed in both of nonHIP-GZ1208K and HIP-GZ1208K alloy. According to analysis, the area number density and the size of ß' precipitate could be adjusted through HIP treatment. The area number density of ß' precipitate increased after HIP treatment when aged at 32 h, and the size of ß' precipitate refined in both of the HIP-GZ1208K alloy aged at 8 h and 32 h. Except the influence of HIP treatment on microstructures, the ultimate tensile strength (UTS) and elongation of nonHIP-GZ1208K alloy also improved after HIP treatment. The UTS of the GZ1208K alloy aged at 8 h increased from 348 MPa (nonHIP-) to 371 MPa (HIP-) and the elongation increased from 2.6% to 4.7%. The density of the nonHIP-GZ1208K alloy increased after HIP treatment, that is to say the casting defects could be eliminated and the compactness of microstructures could be increased under the high pressure of HIP treatment.

The influence of in situ purification system on pathogen in the river fed by the drainage of sewage plant.

An in situ integrated system, consisting of ecological floating islands (EFI), ecological riverbeds (ER), and ecological filter dams (EFD), was built in a ditch only receiving the effluent of sewage plant; the effect of in situ technologies on the distribution of aquatic pathogen was investigated. The results showed the aquatic pathogen decreased along the ditch. Specifically, the relative abundance of Legionella, Aeromonas, and Acinetobacter decreased from 0.032, 0.035, and 0.26 to 0.026%, 0.012%, and 0.08%, respectively. Sedimentation, filtration, and sorption (provided by plant roots and biofilms on substrates) were principal processes for the removal. The nitrogen removal bacteria to prevent the potential risk of eutrophication were also evaluated. The EFI and ER were the dominant sites for Nitrosomonas (34.96%, 32.84%) and Nitrospira (35.74%, 54.73%) enrichment, while EFI and EFD facilitated the enrichment of denitrification bacteria. Notably, the relative abundance of endogenous denitrifiers (DNB-en) (including Dechloromonas at 9.72%, Thermomonas at 0.58%, and Saccharibacteria at 2.55%) exceeded those of exogenous denitrifiers (DNB-ex) (Thauera at 0.20%, Staphylococcus at 0.005%, and Rhodobacter at 0.27%). This study demonstrated that the in situ integrated system was effective in reducing the abundance of pathogens in the drainage channel, and the deficiency of DNB-ex and carbon sources made nitrate removal difficult.

Crosstalk between metabolism and cell death in tumorigenesis.

It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.

Protective autophagy enhances antistress ability through AMPK/ULK1 signaling pathway in human immortalized keratinocytes.

Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear. In this study, we treated immortalized human keratinocytes (HaCaT cells) with low-dose ALA-PDT (0.5 mmol/L, 3 J/cm2). Through RNA-sequencing analysis, we identified that low-dose ALA-PDT modulated autophagy-related pathways in keratinocytes and pinpointed Unc-51-like kinase 1 (ULK1) as a key gene involved. Western blot results revealed that low-dose ALA-PDT treatment upregulated the expression of autophagy-related proteins Beclin-1 and LC3-II/LC3-I ratio. Notably, low-dose ALA-PDT regulated autophagy by inducing an appropriate level of reactive oxygen species (ROS), transiently reducing mitochondrial membrane potential, and decreasing adenosine triphosphate production; all these processes functioned on the AMP-activated protein kinase (AMPK)/ULK1 pathway to activate autophagy. Finally, we simulated external environmental damage using ultraviolet B (UVB) at a dose of 60 mJ/cm2 and observed that low-dose ALA-PDT mitigated UVB-induced cell apoptosis; however, this protective effect was reversed when using the autophagy inhibitor 3-methyladenine. Overall, these findings highlight how low-dose ALA-PDT enhances antistress ability in HaCaT cells through controlling ROS generation and activating the AMPK/ULK1 pathway to arouse cellular autophagy.

Analysis of factors influencing the energy efficiency in Chinese wastewater treatment plants through machine learning and SHapley Additive exPlanations.

Wastewater treatment plants (WWTPs) contribute significantly to the control of pollution in water. However, they are significant energy consumers. Identifying the factors influencing energy consumption is crucial for enhancing the energy efficiency of WWTPs. To address this, the unit energy consumption (UEC) of WWTPs was predicted using machine learning models. In order to accurately evaluate WWTPs' energy utilization efficiency, a comprehensive energy evaluation indicator, UEC (kWh/kg TODremoved) was utilized in this study. Among the prediction models, the eXtreme Gradient Boosting (XGBoost) achieves the highest prediction accuracy. SHapley Additive exPlanations (SHAP) was adopted as the model explanation system, and the results revealed that UEC was negatively affected by TN concentration, which was the most influential factor. The stoichiometry-based model calculation result indicates that the nitrification consumes average 77 % of the overall oxygen demand. SHAP analysis illustrated that the UEC of main technologies decreases with increasing influential factors. Partial dependence plot (PDP) compared average UEC of these technologies and SBR consumed the least amount of energy. The research also indicated that low influent TN concentration is the main problem in China. Consequently, it is imperative to exert efforts in ensuring the influent TN concentration while simultaneously making appropriate adjustments to the treatment process. This study provides valuable implications and methods for retrofitting and upgrading WWTPs.

Safety, tolerability, pharmacokinetics and neutrophil elastase inhibitory effects of Sivelestat: A randomized, double-blind, placebo-controlled single- and multiple-dose escalation study in Chinese healthy subjects.

BACKGROUND AND OBJECTIVE: Neutrophil elastase has been identified as a potential therapeutic target for acute lung injury or acute respiratory distress syndrome, and Sivelestat is a selective, reversible and competitive neutrophil elastase inhibitor. This study was designed to investigate the safety, tolerability, pharmacokinetics and neutrophil elastase inhibitory effects of Sivelestat in healthy Chinese subjects. METHODS: A randomized, double-blind, placebo-controlled single- and multiple-dose escalation clinical trial was carried out. Briefly, healthy volunteers in twelve cohorts with 8 per cohort received 1.0-20.2 mg/kg/h Sivelestat or placebo in an intravenous infusion manner for two hours, and healthy volunteers in four cohorts received two hours intravenous infusion of 2.0-5.0 mg/kg/h Sivelestat or placebo with an interval of twelve hours for seven times. The safety and tolerability were evaluated and serial blood samples were collected for pharmacokinetics and neutrophil elastase inhibitory effects analysis at the specified time-point. RESULTS: A total of 128 subjects were enrolled and all participants completed the study except one. Sivelestat exhibited satisfactory safety and tolerability up to 20.2 mg/kg/h in single-dose cohorts and 5.0 mg/kg/h in multiple-dose cohorts. Even so, more attention should be paid to the safety risks when using high doses. The Cmax and AUC of Sivelestat increased in a dose dependent manner, and Tmax was similar for different dose cohorts. In multiple-dose cohorts, the plasma concentrations reached steady state 48 h after first administration and the accumulation of Cmax and AUC was not obvious. Furthermore, the Cmin_ss of 5.0 mg/kg/h dose cohort could meet the needs of clinical treatment. For some reason, the pharmacodynamics data revealed that the inhibitory effect of Sivelestat on neutrophil elastase content in healthy subjects was inconclusive. CONCLUSION: Sivelestat was safe and well tolerated with appropriate pharmacokinetic parameters, which provided support for more diverse dosing regimen in clinical application. CLINICAL TRIAL REGISTRATION: www.chinadrugtrials.org.cn identifier is CTR20210072.

Emerging role of RNA modification and long noncoding RNA interaction in cancer.

RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.

Detecting and genotyping high-risk human papillomavirus among male patients during 2015-2023 in Beijing, China.

Few studies focused on human papillomavirus (HPV) in male patients. This study aimed to explore the detection rate and genotyping of HPV among male patients in Beijing to provide a reference for formulating prevention strategies for HPV infection. The cross-sectional study was conducted in Beijing Chaoyang Hospital from November 2015 to March 2023. It covered male patients from the urology and dermatology departments. Fifteen high-risk HPV genotypes were detected by the multiplex real-time polymerase chain reaction method. The overall detection rate of HPV was 25.19% (1288/5114, 95% confidence interval [CI] 24.00%-26.38%), of which the single infection rate was 16.99% (869/5114, 95% CI 15.97%-18.05%) and the co-infection rate was 8.19% (419/5114, 95% CI 7.46%-8.98%). The detection rate of HPV was 40.77% (521/1278), 35.58% (58/163), 32.69% (101/309), 31.91% (60/188), 12.63% (299/2367), and 32.35% (131/405) among male patients with balanitis, warts, rash, urethritis, prostatitis, and other urinary inflammation, respectively (P < 0.001). The top five HPV genotypes were HPV-52, HPV-58, HPV-16, HPV-51, and HPV-66. After the first positive HPV test, the proportion of male patients who turned negative was 22.47% within 3 months, 26.40% within 3-6 months, 24.72% within 6-12 months, 17.98% within 12-24 months, and 8.43% more than 24 months. The detection rate of HPV was high among male patients from the urology and dermatology departments in Beijing, which should be considered to develop HPV vaccines with better prevention effects.

Four-Coordinate Co(III) Imide with an Unusually Tilted Terminal Imido Ligand.

We report herein the synthesis and characterization of a terminal Co(III) imido complex supported by an intermediate field N,N,C heteroscorpionate. This chemistry is enabled through the development of an additional member of this ligand type featuring Ph2(CH3)C- substituents, one of which weakly binds and stabilizes Co in the corresponding Co(I) precursor. The Co(III) imide is low-spin with no evidence for thermal population of open-shell excited states. Unusually, the imido ligand in this molecule tilts markedly toward the Calkyl donor. DFT calculations suggest this structural feature to be largely a result of strong Co-C covalency, underscoring the importance of M-C bonding in determining the (electronic) structure of metal centers supported by this class of ligand.