PNPLA3, obesity and heavy alcohol use in cirrhosis patients may exert a synergistic increase hepatocellular carcinoma risk.

BACKGROUND & AIMS: In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors. METHODS: We analyzed data from 1911 patients in two multicenter prospective cohort studies in the U.S. We classified patients according to alcohol consumption (current heavy vs. not current heavy), obesity (body mass index [BMI] ≥30 vs. <30), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs. noncarrier). We examined the independent and joint effects of these risk factors on risk of developing HCC using Cox regression with competing risks. RESULTS: Mean age was 59.6y, 64.3% male, 28.7% Hispanic, 18.3% non-Hispanic Black, 50.9% were obese, 6.2% had current heavy alcohol consumption, and 58.4% harbored at least one PNPLA3 G-allele. 116 patients developed HCC. Compared to PNPLA3 noncarriers without heavy alcohol consumption, HCC risk was 2.65-fold higher (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.20-5.86) for carriers who had current heavy alcohol consumption. Compared to noncarrier patients without obesity, HCC risk was higher (HR, 2.40; 95%CI, 1.33-4.31) for carrier patients who were obese. PNPLA3 and alcohol consumption effect was stronger among patients with viral etiology of cirrhosis (HR, 3.42; 95% CI, 1.31-8.90). PNPLA3 improved 1-year risk prediction for HCC when added to a clinical risk model. CONCLUSIONS: The PNPLA3 variant may help refine risk stratification for HCC in patients with cirrhosis with heavy alcohol consumption or obesity who may need specific preventive measures.

The safety and feasibility Assessment of Overlap Esophagojejunostomy with Self-pulling and Latter Transection Technique in Totally Laparoscopic Total Gastrectomy.

BACKGROUND: This study presents an innovative technique in totally laparoscopic total gastrectomy (TLTG) for Overlap esophagojejunostomy, termed self-pulling and latter transection (Overlap SPLT). It evaluates the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end esophagojejunostomy incorporating self-pulling and latter transection (FETE SPLT). METHODS: From September 2018 to September 2023, this study enrolled 68 gastric cancer patients who underwent totally laparoscopic total gastrectomy (TLTG) with Overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathological characteristics, surgical and postoperative outcomes data for Overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for Overlap SPLT was 25.3 ± 7.4minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0minutes, P = 0.031). Perioperatively, one anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = 0.682). No statistically significant differences were found between the two groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs. 5.8%, P = 0.676). CONCLUSION: The Overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between Overlap SPLT and FETE SPLT, but Overlap SPLT costed one additional stapler cartridge and required a longer duration.

Real-Time Monitoring of Tyrosine Hydroxylase Activity with a Ratiometric Fluorescent Probe.

Parkinson's disease (PD) represents the second most widespread neurodegenerative disease, and early monitoring and diagnosis are urgent at present. Tyrosine hydroxylase (TH) is a key enzyme for producing dopamine, the levels of which can serve as an indicator for assessing the severity and progression of PD. This renders the specific detection and visualization of TH a strategically vital way to meet the above demands. However, a fluorescent probe for TH monitoring is still missing. Herein, three rationally designed wash-free ratiometric fluorescent probes were proposed. Among them, TH-1 exhibited ideal photophysical properties and specific dual-channel bioimaging of TH activity in SH-SY5Y nerve cells. Moreover, the probe allowed for in vivo imaging of TH activity in zebrafish brain and living striatal slices of mice. Overall, the ratiometric fluorescent probe TH-1 could serve as a potential tool for real-time monitoring of PD in complex biosystems.

Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy.

Photodynamic therapy (PDT) has emerged as a promising approach for tumor treatment. However, traditional type II PDT faces limitations due to its oxygen-dependent nature. Type-I photosensitizers (PSs) exhibit superiority over conventional type-II PSs owing to their diminished oxygen dependence. Nevertheless, designing effective type-I PSs remains a significant challenge. In this work, we provide a novel strategy to tune the PDT mechanism of an excited photosensitizer through aryl substituent engineering. Using S-rhodamine as the base structure, three PSs were synthesized by incorporating phenyl, furyl, or thienyl groups at the meso position. Interestingly, furyl- or thienyl-substituted S-rhodamine are type-I-dominated PSs that produce O2˙-, while phenyl S-rhodamine results in O2˙- and 1O2 through type-I and type-II mechanisms, respectively. Experimental analyses and theoretical calculations showed that the introduction of a five-membered heterocycle at the meso position promoted intersystem crossing (ISC) and electron transfer, facilitating the production of O2˙-. Furthermore, furyl- or thienyl-substituted S-rhodamine exhibited high phototoxicity at ultralow concentrations. Thienyl-substituted S-rhodamine showed promising PDT efficacy against hypoxic solid tumors. This innovative strategy provides an alternative approach to developing new type-I PSs without the necessity for creating entirely new skeletons.

Treatment of hemolymphangioma by robotic surgery: A case report.

BACKGROUND: Hemolymphangioma of the jejunum is rare and lacks clinical specificity, and can manifest as gastrointestinal bleeding, abdominal pain, and intestinal obstruction. Computed tomography, magnetic resonance imaging, and other examinations show certain characteristics of the disease, but lack accuracy. Although capsule endoscopy and enteroscopy make up for this deficiency, the diagnosis also still requires pathology. CASE SUMMARY: A male patient was admitted to the hospital due to abdominal distension and abdominal pain, but a specific diagnosis by computed tomography examination was not obtained. Partial resection of the small intestine was performed by robotic surgery, and postoperative pathological biopsy confirmed the diagnosis of hemolymphangioma. No recurrence in the follow-up examination was observed. CONCLUSION: Robotic surgery is an effective way to treat hemolymphangioma through minimally invasive techniques under the concept of rapid rehabilitation.

Reshaped DNA methylation cooperating with homoeolog-divergent expression promotes improved root traits in synthesized tetraploid wheat.

Polyploidization is a major event driving plant evolution and domestication. However, how reshaped epigenetic modifications coordinate gene transcription to generate phenotypic variations during wheat polyploidization is currently elusive. Here, we profiled transcriptomes and DNA methylomes of two diploid wheat accessions (SlSl and AA) and their synthetic allotetraploid wheat line (SlSlAA), which displayed elongated root hair and improved root capability for nitrate uptake and assimilation after tetraploidization. Globally decreased DNA methylation levels with a reduced difference between subgenomes were observed in the roots of SlSlAA. DNA methylation changes in first exon showed strong connections with altered transcription during tetraploidization. Homoeolog-specific transcription was associated with biased DNA methylation as shaped by homoeologous sequence variation. The hypomethylated promoters showed significantly enriched binding sites for MYB, which may affect gene transcription in response to root hair growth. Two master regulators in root hair elongation pathway, AlCPC and TuRSL4, exhibited upregulated transcription levels accompanied by hypomethylation in promoter, which may contribute to the elongated root hair. The upregulated nitrate transporter genes, including NPFs and NRTs, also are significantly associated with hypomethylation, indicating an epigenetic-incorporated regulation manner in improving nitrogen use efficiency. Collectively, these results provided new insights into epigenetic changes in response to crop polyploidization and underscored the importance of epigenetic regulation in improving crop traits.

Food and environmental safety monitoring platform based on Tb(III) functionalized HOF hybrids for ultrafast detection of thiabendazole and 2-chlorophenol.

Development of efficient and intelligent method for detecting harmful agrochemicals in resource-limited settings remains an urgent need to ensure food and environmental safety. Herein, a novel dual-emitting Tb3+-modified hydrogen-bonded organic framework (Tb@TBTC, TBTC is the ligand of HOF-TBTC.) with visible green fluorescence has been prepared through coordination post-synthetic modification. Tb@TBTC can be designed as a fluorescence sensor for the identification of two harmful carcinogenic pesticides, thiabendazole (TBZ) and 2-chlorophenol (2-CP) with high sensitivity, high efficiency and excellent selectivity. Tb@TBTC can also adsorb 2-CP with high adsorption rate. In realistic fruit juice and river water samples, the detection limits of Tb@TBTC toward TBZ and 2-CP are as low as 2.73 µM and 2.18 µM, respectively, demonstrating the feasibility in practical application. Furthermore, an intelligent real-time and on-site monitoring platform for 2-CP detection is constructed based on Tb@TBTC-agarose hydrogel films with the assistance of back propagation neural network, which can efficiently and accurately determine the concentration of 2-CP from fluorescence images through human-machine interaction. This work presents a facile pathway to prepare Tb@HOF fluorescent sensor for food and ecological environment safety, which is highly promising for preventing human disease and improving global public health.

Insights into the impact of modification methods on the structural characteristics and health functions of pectin: A comprehensive review.

Pectin is a complex polysaccharide that is widely present in plant cells and has multiple physiological functions. However, most pectin exists in the form of protopectin, which has a large molecular weight and cannot be fully absorbed and utilized in the human gut to exert its effects. The significant differences in the structure of different sources of pectin also limited their application in the food and medical fields. In order to achieve greater development and utilization of pectin functions, this paper reviewed several commonly used methods for pectin modification from physical, chemical, and biological perspectives, and elaborated on the relationship between these modification methods and the structure and functional properties of pectin. At the same time, the functional characteristics of modified pectin and its application in medical health, such as regulating intestinal health, anticancer, anti-inflammatory, and drug transport, were reviewed, so as to provide a theoretical basis for targeted modification of pectin and the development of new modified pectin products.

The relationship between trajectories of renal oxygen saturation and acute kidney injury: a prospective cohort study with a secondary analysis.

BACKGROUND: Acute kidney injury (AKI) is a major postoperative consequence, affecting prognosis of older patients. Effective prediction or intervention to predict or prevent the incidence of AKI is currently unavailable. AIMS: Dynamic changes of renal tissue oxygen saturation (RSO2) during surgery process are understudied and we intended to explore the distinct trajectories and associations with postoperative AKI. METHODS: This was a secondary analysis including data for older patients who underwent open hepatectomy surgery with informed consent. Latent class mixed models (LCMM) method was conducted to generate trajectories of intraoperative renal tissue RSO2 through different time points. The primary outcome was postoperative 7-day AKI. The univariate and multivariate regression analysis were performed to identify the relationship between distinct trajectories of renal tissue RSO2 and the risk of AKI. Meanwhile, the prediction efficacy of renal tissue RSO2 at different time points was compared to find potential intervention timing. RESULTS: Postoperative AKI occurred in 14 (15.2%) of 92 patients. There are two distinct renal tissue RSO2 trajectories, with 44.6% generating "high-downwards" trajectory and 55.4% generating "consistently-high" trajectory. Patients with "high-downwards" trajectory had significantly higher risk of postoperative AKI than another group (Unadjusted OR [Odds Ratio] = 3.790, 95% CI [Confidence Interval]: 1.091-13.164, p = 0.036; Adjusted OR = 3.973, 95% CI 1.020-15.478, p = 0.047, respectively). Predictive performance was 71.4% sensitivity and 60.3% specificity for "high-downwards" trajectory of renal tissue RSO2 to identify AKI. Furthermore, the renal tissue RSO2 exhibited the lowest level and the best results in terms of the sensitivity during the hepatic occlusion period, may be considered as a "time of concern". CONCLUSIONS: Older patients undergoing hepatectomy may show high-downwards trajectory of renal tissue RSO2, indicating a higher risk of AKI, and the lowest level was identified during the hepatic occlusion period. These findings may help to provide potential candidates for future early recognition of deterioration of kidney function and guide interventions.

Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.

Withania somnifera root extract inhibits MGO-induced skin fibroblast cells dysfunction via ECM-integrin interaction.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal, known as Ashwagandha, has long been used in traditional medicine in Ayurveda, India, a representative adaptogen. The main active constituents of W. somnifera are withanolides, and the root is often used as a medicine with a wide range of pharmacological activities, which can be used to treat insomnia, neurasthenia, diabetes mellitus and skin cancer. AIM OF THE STUDY: Whole-component qualitative and quantitative analyses were performed on W. somnifera. We explored the ameliorative effect of the adaptogen representative plant W. somnifera on the senescence events of MGO-injured fibroblasts and its action mechanism and verified the hypotheses that WS can inhibit the accumulation of AGEs and regulate the dynamic balance among the components of the ECM by modulating the expression of integrin ß1 receptor; as a result, WS maintains cellular behavioural and biological functions in a normal range and retards the aging of skin from the cellular level. MATERIALS AND METHODS: In this study, the components of WS were first qualitatively and quantitatively analysed by HPLC fingerprinting and LC-MS detection. Second, a model of MGO-induced injury of CML-overexpressing fibroblasts was established. ELISA was used to detect CML expression and the synthesis of key extracellular matrix ECM protein components COL1, FN1, LM5 and TNC synthesis; CCK-8 was used to detect cell viability; EDU was used to detect cell proliferation capacity; fluorescence was used to detect cell adhesion capacity; and migration assay were used to detect cell migration capacity; qRT-PCR was used to detect the regulatory pathway TGF-ß1 and MMP-2, MMP-9 in ECMs; immunofluorescence was used to detect the expression of ITGB1; and WB was used to detect the expression of COL1, FN1, LM5, Tnc, TGF-ß1, MMP-2, MMP-9 and ITGB1. RESULTS: In total, 27 active ingredients were analysed from WS, which mainly consisted of withanolide components, such as withaferin A and withanolide A. Based on the model of MGO-induced fibroblast senescence injury, WS significantly inhibited CML synthesis. By up-regulating the expression of integrin ß1, it upregulated the expression of the TGF-ß1 gene, which is closely related to the generation of ECMs, downregulated the expression of the MMP-2 and MMP-9 genes, which are closely related to the degradation of ECMs, maintained the dynamic balance of the four types of ECMs, and improved cell viability as well as proliferation, migration and adhesion abilities. CONCLUSIONS: WS can prevent cellular behavioural dysfunction and delay skin ageing by reducing the accumulation of CML, upregulating the expression of the ITGB1 receptor, maintaining the normal function of ECM-integrin receptor interaction and preventing an imbalance between the production and degradation of protein components of ECMs. The findings reported in this study suggest that WS as a CML inhibitor can modulate ECM-integrin homeostasis and has great potential in the field of aging retardation.

Association of sleep quality on the night of operative day with postoperative delirium in elderly patients: A prospective cohort study.

BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65 years or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P  = 0.005). Subgroup analysis revealed that age 65-75 years; male sex; ASA III and IV; haemoglobin more than 12 g l -1 ; intra-operative hypotension; surgical duration more than 120 min; and education 9 years or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.

Public Knowledge and Awareness of Anesthesiology and Anesthesiologists in China: A Cross-Sectional National Survey of 1 Million Participants.

BACKGROUND: In the past 20 years, anesthesiology has become one of the most advanced specialties and has undergone rapid development. However, public awareness regarding anesthesiology and anesthesiologists is limited, especially in developing countries. It is important for anesthesiologists to make the public aware of their role during surgery. Therefore, a nationwide survey was set up to investigate public awareness of anesthesiology and anesthesiologists in China. METHOD: A cross-sectional nationwide survey was performed from June 2018 to June 2019 in 34 provinces, municipalities, and autonomous regions across China and an overseas region. The questionnaires of the survey were divided into 2 main parts: general items and research items. General items included the demographic characteristics of the participants; research items consisted of 10 questions about the public's awareness of anesthesiologists and anesthesiology. Data quality control was undertaken by the investigation committee throughout the survey process. RESULTS: The nationwide survey enrolled 1,001,279 participants (male, 40.7%). We found that most of the participants regarded anesthesiologists as doctors. However, public knowledge of anesthesiologists' work and duties during surgery was quite low, with correct response rate ranging from 16.5% to 52.9%, and anesthesiologist responsibilities were often mistakenly attributed to surgeons or nurses. It is disappointing that more than half of participants still thought that, once the patient fell asleep after receiving anesthetics, the anesthesiologist could leave the operating room. Finally, the correct response rate was positively correlated with the economic levels of the regions. CONCLUSIONS: Public awareness regarding anesthesiology and anesthesiologists in China remains inadequate. Due to the biases and characteristics of the participants, the actual situation of the general Chinese public is likely even worse than reflected here. Therefore, extensive measures should be undertaken to improve public knowledge of anesthesiology and anesthesiologists.

Risk factors prediction of 6-month mortality after noncardiac surgery of older patients in China: a multicentre retrospective cohort study.

BACKGROUND: Identifying the risk factors associated with perioperative mortality is crucial, particularly in older patients. Predicting 6-month mortality risk in older patients based on large datasets can assist patients and surgeons in perioperative clinical decision-making. This study aimed to develop a risk prediction model of mortality within 6 months after noncardiac surgery using the clinical data from 11 894 older patients in China. MATERIALS AND METHODS: A multicentre, retrospective cohort study was conducted in 20 tertiary hospitals. The authors retrospectively included 11 894 patients (aged ≥65 years) who underwent noncardiac surgery between April 2020 and April 2022. The least absolute shrinkage and selection operator model based on linear regression was used to analyse and select risk factors, and various machine learning methods were used to build predictive models of 6-month mortality. RESULTS: The authors predicted 12 preoperative risk factors associated with 6-month mortality in older patients after noncardiac surgery. Including laboratory-associated risk factors such as mononuclear cell ratio and total blood cholesterol level, etc. Also including medical history associated risk factors such as stroke, history of chronic diseases, etc. By using a random forest model, the authors constructed a predictive model with a satisfactory accuracy (area under the receiver operating characteristic curve=0.97). CONCLUSION: The authors identified 12 preoperative risk factors associated with 6-month mortality in noncardiac surgery older patients. These preoperative risk factors may provide evidence for a comprehensive preoperative anaesthesia assessment as well as necessary information for clinical decision-making by anaesthesiologists.

High-humidity hot-air impingement blanching conditions for the inhibition of potato-browning enzymes and for quality retention.

BACKGROUND: Potato is an important non-cereal crop. It provides carbohydrates, a major source of energy in the human diet. Blanching during the processing of fresh fruits and vegetables is essential for their preservation. High-humidity hot-air impingement blanching (HHAIB) is a promising emerging technology for pretreating different food materials. This research aimed to identify the optimum HHAIB conditions for the inhibition of potato-browning enzymes, maintaining their nutritional and physical quality, and to compare this with conventional hot-water blanching (HWB). RESULTS: Polyphenol oxidase (PPO) inactivation, total phenol content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, color, textural attributes, thermal properties, microstructure, and particles crystallinity were evaluated. The relative humidity (RH), temperature, and duration of HHAIB required for PPO inactivation (2.59%) were 50%, 105 °C, and 4 min, respectively, which resulted in a complete gelatigination of potato starches, based on the thermal properties and the microstrcture of the blanched potatoes. These conditions led to improvements in TPC to 312.54 µg GAE.g-1 FP, DPPH scavenging to 1.99 µmol TE.g-1 FP, as well as enhancements in color and crystallinity. When HHAIB was conducted at lower temperatures (85 and 95 °C) there were negative effects on the blanched potatoes' color and crystallinity, along with a non-safe level of PPO activity. CONCLUSION: High-humidity hot-air impingement blanching was superior to HWB, inhibiting PPO, maintaining nutrients, and preserving physical properties, especially under the optimum conditions revealed by the principal component analysis. It provides an excellent technique for blanching and pretreating potatoes, preserving them, and maintaining their quality. © 2023 Society of Chemical Industry.

An organic state trace element solution for rheumatoid arthritis treatment by modulating macrophage phenotypic from M1 to M2.

Trace elements (TEs) are essential for the treatment of rheumatoid arthritis (RA). This study aimed to prepare a TEs solution enriched with various organic states to evaluate its preventive, therapeutic effects, and mechanism of action in RA and to provide a treatment method for RA treatment. The TEs in natural ore were extracted and added to 0.5% (W/V) L-alanyl-L-glutamine (LG) to obtain a TEs solution (LG-WLYS), which was examined for its concentration and quality. The antioxidant properties and effects of LG-WLYS on cell behavior were evaluated at the cellular level. The preventive and therapeutic effects and mechanism of action of LG-WLYS in rats with RA were explored. The LG-WLYS solution was clear, free from visible foreign matter, and had a pH of 5.33 and an osmolality of 305.67 mOsmol/kg. LG-WLYS inhibited cell migration and angiogenesis. LG-WLYS solution induced macrophages to change from M1-type to M2-type, increased the content of antioxidant enzymes (glutathione, superoxide dismutase, and IL-10), decreased the levels of nitric oxide, malondialdehyde, TNF-α, IL-1ß, IL-6, COX-2, and iNOs, scavenging reactive oxygen species from the lesion site, inhibiting the apoptosis of chondrocytes, regulating inflammatory microenvironment, and decreasing inflammation response to exert the therapeutic effect for RA. In conclusion, LG-WLYS has outstanding therapeutic and preventive effects against RA and has enormous potential for further development.

Preoperative prognostic nutritional index predicts postoperative delirium in aged patients after surgery: A matched cohort study.

OBJECTIVE: Prognostic nutritional index (PNI) is an indicator to evaluate the nutritional immune status of patients. This study aimed to assess whether preoperative PNI could predict the occurrence of postoperative POD in aged patients undergoing non-neurosurgery and non-cardiac surgery. METHOD: The aged patients undergoing non-neurosurgery and non-cardiac surgery between January 2014 and August 2019 were included in the retrospective cohort study. The correlation between POD and PNI was investigated by univariate and multivariable logistic regression analysis, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and subgroup analysis. RESULTS: In the cohort (n = 29,814), the cutoff value of PNI was 46.01 determined by the receiver operating characteristic (ROC) curve. In univariate and three multivariable regression analysis, the ORs of PNI ≤ 46.01 was 2.573(95% CI:2.261-2.929, P < 0.001),1.802 (95% CI:1.567-2.071, P < 0.001),1.463(95% CI:1.246-1.718, P < 0.001),1.370(95% CI:1.165-1.611, P < 0.001). In the PSM model and IPTW model, the ORs of PNI ≤ 46.01 were 1.424(95% CI:1.172-1.734, P < 0.001) and 1.356(95% CI:1.223-1.505, P < 0.001). CONCLUSION: The PNI was found to have a predictive value for POD in patients undergoing non-neurosurgery and non-cardiac surgery. Improving preoperative nutritional status may be beneficial in preventing POD for aged patients.

Liver macrophages and sinusoidal endothelial cells execute vaccine-elicited capture of invasive bacteria.

Vaccination has substantially reduced the morbidity and mortality of bacterial diseases, but mechanisms of vaccine-elicited pathogen clearance remain largely undefined. We report that vaccine-elicited immunity against invasive bacteria mainly operates in the liver. In contrast to the current paradigm that migrating phagocytes execute vaccine-elicited immunity against blood-borne pathogens, we found that invasive bacteria are captured and killed in the liver of vaccinated host via various immune mechanisms that depend on the protective potency of the vaccine. Vaccines with relatively lower degrees of protection only activated liver-resident macrophage Kupffer cells (KCs) by inducing pathogen-binding immunoglobulin M (IgM) or low amounts of IgG. IgG-coated pathogens were directly captured by KCs via multiple IgG receptors FcγRs, whereas IgM-opsonized bacteria were indirectly bound to KCs via complement receptors of immunoglobulin superfamily (CRIg) and complement receptor 3 (CR3) after complement C3 activation at the bacterial surface. Conversely, the more potent vaccines engaged both KCs and liver sinusoidal endothelial cells by inducing higher titers of functional IgG antibodies. Endothelial cells (ECs) captured densely IgG-opsonized pathogens by the low-affinity IgG receptor FcγRIIB in a "zipper-like" manner and achieved bacterial killing predominantly in the extracellular milieu via an undefined mechanism. KC- and endothelial cell-based capture of antibody-opsonized bacteria also occurred in FcγR-humanized mice. These vaccine protection mechanisms in the liver not only provide a comprehensive explanation for vaccine-/antibody-boosted immunity against invasive bacteria but also may serve as in vivo functional readouts of vaccine efficacy.

MSDE-Net: A Multi-Scale Dual-Encoding Network for Surgical Instrument Segmentation.

Minimally invasive surgery, which relies on surgical robots and microscopes, demands precise image segmentation to ensure safe and efficient procedures. Nevertheless, achieving accurate segmentation of surgical instruments remains challenging due to the complexity of the surgical environment. To tackle this issue, this paper introduces a novel multiscale dual-encoding segmentation network, termed MSDE-Net, designed to automatically and precisely segment surgical instruments. The proposed MSDE-Net leverages a dual-branch encoder comprising a convolutional neural network (CNN) branch and a transformer branch to effectively extract both local and global features. Moreover, an attention fusion block (AFB) is introduced to ensure effective information complementarity between the dual-branch encoding paths. Additionally, a multilayer context fusion block (MCF) is proposed to enhance the network's capacity to simultaneously extract global and local features. Finally, to extend the scope of global feature information under larger receptive fields, a multi-receptive field fusion (MRF) block is incorporated. Through comprehensive experimental evaluations on two publicly available datasets for surgical instrument segmentation, the proposed MSDE-Net demonstrates superior performance compared to existing methods.

Molecular Engineering of Sulfone-Xanthone Chromophore for Enhanced Fluorescence Navigation.

Enriching the palette of high-performance fluorescent dyes is vital to support the frontier of biomedical imaging. Although various rhodamine skeletons remain the premier type of small-molecule fluorophores due to the apparent high brightness and flexible modifiability, they still suffer from the inherent defect of small Stokes shift due to the nonideal fluorescence imaging signal-to-background ratio. Especially, the rising class of fluorescent dyes, sulfone-substituted xanthone, exhibits great potential, but low chemical stability is also pointed out as the problem. Molecular engineering of sulfone-xanthone to obtain a large Stokes shift and high stability is highly desired, but it is still scarce. Herein, we present the combination modification method for optimizing the performance of sulfone-xanthone. These redesigned fluorescent skeletons owned greatly improved stability and Stokes shift compared with the parent sulfone-rhodamine. To the proof of bioimaging capacity, annexin protein-targeted peptide LS301 was introduced to the most promising dyes, J-S-ARh, to form the tumor-targeted fluorescent probe, J-S-LS301. The resulting probe, J-S-LS301, can be an outstanding fluorescence tool for the orthotopic transplantation tumor model of hepatocellular carcinoma imaging and on-site pathological analysis. In summary, the combination method could serve as a basis for rational optimization of sulfone-xanthone. Overall, the chemistry reported here broadens the scope of accessible sulfone-xanthone functionality and, in turn, enables to facilitate the translation of biomedical research toward the clinical domain.