[Distribution and Drug Resistance Characteristics of Pathogenic Bacteria in the Elderly Population in China in 2021]. / 2021å¹´ä¸­å›½è€å¹´äººç¾¤æ„ŸæŸ“ç— åŽŸèŒåˆ†å¸ƒå’Œè€è¯æ€§ç‰¹å¾.

Objective: To study the distribution and drug resistance characteristics of pathogenic bacteria in the elderly population of China by collecting and analyzing the standardized case data on the pathogens of infections in elderly patients, and to facilitate the establishment of a standardized layered surveillance system for pathogenic bacteria in China. Methods: We collected the case data of elderly patients (≥65 years old) from 62 sentinel hospitals across the country in 2021. Then, we statistically analyzed the data by patient age, their geographical region, the distribution of pathogenic bacteria, and the drug resistance characteristics of main pathogens. Results: A total of 3468 cases from across the country were included in the study. The top three sources of patients were the intensive care unit (13.2%), the department of respiratory medicine (11.2%), and the department of general surgery (8.4%). The top three types of specimens were urine (25.5%), sputum (20.6%), and blood (18.7%). A total of 3468 strains of pathogens were isolated, among which, 78.9% were gram-negative bacteria and 21.1% were gram-positive bacteria. The top five types of bacteria were Escherichia coli (20.9%), Klebsiella pneumoniae (18.3%), Pseudomonas aeruginosa (11.2%), Staphylococcus aureus (9.0%), and Acinetobacter baumannii (7.0%). The isolation rates of common important drug-resistant bacteria were 38.0% for methicillin-resistant Staphylococcus aureus (MRSA), 68.7% for carbapenem-resistant Acinetobacter baumannii (CRAB), and 38.2% for carbapenem-resistant Pseudomonas aeruginosa (CRPA), 20.1% for carbapenem-resistant Klebsiella pneumoniae (CRKP), 5.2% for carbapenem-resistant Escherichia coli (CRECO), and 2.1% for vancomycin-resistant Enterococcus (VRE). There were differences in the isolation rates of CRAB and CRKP in clinical care in the elderly population in seven geographical regions of China (P<0.05). Klebsiella pneumoniae is the most important pathogen in the elderly population ≥85 years old, and the isolation rates of CRKP showed significant differences in different age groups (P<0.05). Conclusion: There are significant differences in the drug resistance of pathogenic bacteria in the elderly populations of different regions and age groups in China. Therefore, monitoring the distribution and drug resistance of pathogenic bacteria in the elderly population and formulating targeted treatment plans according to the characteristics of the specific regions and age groups are of great significance to the improvement in the treatment outcomes and prognosis of the elderly population.

Dysregulated T-cell homeostasis and decreased CD30+ Treg proliferating in aplastic anemia.

Aplastic anemia (AA) is an autoimmune hematopoietic disease mediated by autoreactive T cells leading to bone marrow failure. However, the precise role of autoreactive T cells in the development of AA is not fully understood, hindering the advancement of therapeutic and diagnostic strategies. In this study, we conducted a single-cell transcriptome analysis of CD8+ T cells, conventional CD4+ T (CD4+ Tconv) cells, and Treg cells, to elucidate the potential disruption of T cell homeostasis in patients with AA. We identified changes in CD4+ Tconv cells, including loss of homeostasis in naïve and memory cells and increased differentiation potential in T helper type 1 (TH1), T helper type 2 (TH2), and T helper type 17 (TH17) cells. Additionally, we identified naïve and memory CD8+ T cells that were enforced into an effector state. CD127 is an ideal surface marker for assessing the immune state of CD8+ T cells，as identified by flow cytometry. Abnormal expression of TNFSF8 has been observed in AA and other autoimmune diseases. Flow cytometry analysis revealed that TNFRSF8 (CD30), a receptor for TNFSF8, was predominantly present in human Treg cells. Importantly, patients with AA have a decreased CD30+ Treg subset. RNA-sequencing analysis revealed, that the CD30+ Treg cells are characterized by high proliferation and a remarkable immunosuppressive phenotype. Taken, together, we propose that abnormal TNFSF8/TNFRSF8 signaling is involved in dysfunctional T cell immunity by increasing the destruction of CD30+ Treg cells.

Sleep-aiding music therapy for insomnia: Exploring EEG functional connectivity of sleep-related attentional bias.

STUDY OBJECTIVES: This study aimed to investigate the relationship between sleep-aiding music and sleep-related attentional bias based on electroencephalography (EEG) functional connectivity (FC) in patients with insomnia disorder (ID), to evaluate the effectiveness of music in aiding sleep. METHOD: This study included 30 participants, comprising 15 patients with ID and 15 healthy controls (HCs). Six types of music were selected for sleep aid, and a dot-probe task based on sleep-related attentional bias was utilized to collect behavioral and EEG data. Vigilance bias and disengagement bias were measured using reaction time and EEG FC. Differences in sleep-related attentional bias before and after the intervention of music were explored to evaluate the sleep-aiding effects and identify EEG biomarkers. RESULTS: Compared with HCs, patients with ID showed decreased sleep-related attentional bias of EEG FC between occipital-central and temporal-frontal lobes. Among the six types of music, International Standard Sleep Aid and Lullaby had a greater impact on decreasing vigilance bias in the ID group. Additionally, the International Standard Sleep Aid and Nature Sound were more effective in decreasing disengagement bias in the ID group. This study also examined the resting-state EEG FC of patients with ID before and after the intervention of music. The results showed that the FC in the temporal, frontal, and occipital lobes significantly differed before and after the intervention of music, especially with the use of International Standard Sleep Aid, Lullaby, and Alpha Sound Wave. However, it is worth noting that these three types of music showed no similarities in EEG FC, in contrast to the result of sleep-related attentional bias of EEG FC. CONCLUSION: This study found that the sleep-related attentional bias of EEG FC has more distinct characteristics when compared to resting-state EEG FC. The results suggest that the sleep-related attentional bias of EEG FC could be a potential biomarker for assessing the sleep-aiding effect of music interventions. International Standard Sleep Aid was the most effective for patients with ID among six types of sleep-aiding music. These findings could facilitate the development of personalized therapies for patients with ID. CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Register, http://www.chictr.org.cn, ID: ChiCTR2400081608.

Soil keystone viruses are regulators of ecosystem multifunctionality.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

Similar usage of T-cell receptor ß-chain between tumor and adjacent normal tissue in hepatocellular carcinoma.

BACKGROUND: In this study, we comprehensively profiled the T-cell receptor (TCR) repertoire of the tumor and adjacent normal tissue in patients with HBV-associated hepatocellular carcinoma (HCC) and determined the baseline characteristics and clinical significance of TCR. METHODS: High-throughput sequencing was used to determine the profile of complementarity-determining region 3 (CDR3) of the TCR-ß chain variable (TRBV) in the tumor and normal tissue samples of 14 HCC patients. At the same time, TRBV diversity and differences in expression between tumor and normal tissues were investigated. The cumulative frequency of top 100 CDR3 (CF100), clonality, and Shannon entropy as indices to evaluate diversity, RESULTS: The diversity of TRBV CDR3 showed no significant difference between tumor and normal tissues. Of the 58 V gene segments in TRBV, TRBV16 and TRBV7-6 had a significantly higher frequency in the tumor group than in the normal group (p < 0.05). The frequency of 14 J gene segments showed no significant difference between tumor and normal tissues. In contrast, the frequency of 22 TRBVx/BJx combinations was significantly higher in the tumor than in the normal tissue. In addition, the length and type of TRBV CDR3 were similar in tumor and normal tissues, and a Gaussian distribution was observed in both groups. CONCLUSION: This study provided a large amount of information about the TCR lineage in HBV-associated HCC, laying the foundation for further research. In addition, the fact that the immune repertoire (TRBV CDR3) hardly differs between tumor and adjacent normal tissue provides a new clue for exploring the mechanism of the liver as an organ with immune privileges.

Ru(II)-Catalyzed C-H Amination of 1,2,3-Benzotriazinones with Azide Compounds.

A Ru(II)-catalyzed directed C-H amination of 1,2,3-benzotriazinones with azide compounds has been reported. The reaction has a wide substrate scope of organic azides with good results and represents a useful pathway to the construction of versatile heterocyclic amino products. In addition, the method can be used for the phthalazinones, highlighting the synthetic practicability of the strategy.

Surface Structure Reformulation from CuO to Cu/Cu(OH)2 for Highly Efficient Nitrate Reduction to Ammonia.

Electrochemical conversion of nitrate (NO3 -) to ammonia (NH3) is a potential way to produce green NH3 and remediate the nitrogen cycle. In this paper, an efficient catalyst of spherical CuO made by stacking small particles with oxygen-rich vacancies is reported. The NH3 yield and Faraday efficiency are 15.53 mg h-1 mgcat -1 and 90.69%, respectively, in a neutral electrolyte at a voltage of -0.80 V (vs. reversible hydrogen electrode). The high activity of the electrodes results from changes in the phase and structure during electrochemical reduction. Structurally, there is a shift from a spherical structure with dense accumulation of small particles to a layered network structure with uniform distribution of small particles stacked on top of each other, thus exposing more active sites. Furthermore, in terms of phase, the electrode transitions from CuO to Cu/Cu(OH)2. Density functional theory calculations showed that Cu(OH)2 formation enhances NO3- adsorption. Meanwhile, the Cu(OH)2 can inhibit the competing hydrogen evolution reaction, while the formation of Cu (111) crystal surfaces facilitates the hydrogenation reaction. The synergistic effect between the two promotes the NO3- to NH3. Therefore, this study provides a new idea and direction for Cu-based oxides in electrocatalytic NH3 production.

Anchored PKA synchronizes adrenergic phosphoregulation of cardiac Cav1.2 channels.

Adrenergic modulation of voltage gated Ca2+ currents is a context specific process. In the heart Cav1.2 channels initiate excitation-contraction coupling. This requires protein kinase A (PKA) phosphorylation of the small GTPase Rad (Ras associated with diabetes) and involves direct phosphorylation of a1 subunit of the Cav1.2 at Ser1700. A contributing factor is the proximity of PKA to the channel through association with A-kinase anchoring proteins (AKAPs). Disruption of PKA anchoring by the disruptor peptide AKAP-IS prevents up-regulation of Cav1.2 currents in tsA-201 cells. Biochemical analyses demonstrate that Rad does not function as an A-kinase anchoring protein. Electrophysiological recording shows that channel mutants lacking phosphorylation sites (Cav1.2 STAA) lose responsivity to the second messenger cAMP. Measurements in cardiomyocytes isolated from Rad-/- mice show that adrenergic activation of Cav1.2 is attenuated but not completely abolished. Whole animal electrocardiography studies reveal that cardiac selective Rad knockout mice exhibited higher baseline left-ventricular ejection fraction (EF), greater fractional shortening (FS), and increased heart rate as compared to control animals. Yet, each parameter of cardiac function was slightly elevated when Rad-/- mice were treated with the adrenergic agonist isoproterenol. Thus, phosphorylation of Cav1.2 and dissociation of phospho-Rad from the channel are local cAMP responsive events that act in concert to enhance L-type calcium currents. This convergence of local PKA regulatory events at the cardiac L-type calcium channel may permit maximal ß-adrenergic influence on the fight-or-flight response.

Efficacy and safety of chiauranib in a combination therapy in platinum-resistant or refractory ovarian cancer: a multicenter, open-label, phase Ib and II study.

BACKGROUND: Platinum-resistant or refractory ovarian cancer is a highly lethal gynecologic disease with limited treatment options. Chiauranib is a novel small-molecule selective inhibitor, which could effectively target multiple pathways including Aurora B and CSF-1R to inhibit cell cycle process and improve anti-tumor immune function, as long as VEGF pathway for tumor extinction. METHODS: A phase II study was sequentially conducted after a phase Ib monotherapy study to evaluate the efficacy of chiauranib combined with chemotherapy. Chinese patients with recurrent ovarian cancer were enrolled. Eligible patients received chiauranib combined with a maximum of six cycles of chemotherapy: etoposide (CE group) or weekly-paclitaxel (CP group). Patients, who exhibited a complete or partial response, or stable disease following combo treatment, progressed to maintenance phase to receive chiauranib monotherapy. Primary endpoint was progression-free survival (PFS) according to RECIST v1.1. RESULTS: From November 2017 to March 2019, 25 patients were enrolled in a phase 1b study and a median PFS of 3.7 months (95% CI 1.8-NE) was achieved by chiauranib monotherapy. From July 2019 to December 2020, a total of 47 patients were enrolled in the phase II study. One CP patient did not receive the study drugs, and three patients withdrew before the first tumor assessment. Thus, 43 patients (CE group: 22 patients; CP group: 21 patients) were included in the evaluation. The median PFS was 5·4 months (95% CI 2·8-5·6) and 5·6 months (95% CI 3·4-7·0), respectively. CONCLUSIONS: This was the first study to evaluate chiauranib, a novel multi-targeted kinase inhibitor in patients with ovarian cancer. The administration of chiauranib along with etoposide or weekly-paclitaxel significantly enhanced the efficacy with manageable adverse events. This warrants further clinical studies on this novel treatment. A phase III study is promising and ongoing. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT03901118 (phase II) and NCT03166891 (phase Ib).

Initial solution pH value for the construction of a 3D hydroxyapatite via the trisodium citrate-assisted hydrothermal route.

In this study, a trisodium citrate (TSC)-assisted hydrothermal method is utilized to prepare three-dimensional hydroxyapatite (3D HA). Understanding the role of TSC in the preparation of 3D HA crystals may provide valuable methods to design advanced biomaterials. As one of the indexes of solution supersaturation, the initial pH (ipH) value can not only directly affect the nucleation rate, but also affect the growth of HA crystals. In this work, the effect of the ipH on the microstructure, particle size distribution, and specific surface area of the 3D HA is explored. Results showed that the morphology of 3D HA transformed from a bundle to a dumbbell ball and then a dumbbell with an increase in the ipH. A corresponding mechanism of such a structural evolution was proposed, providing inspiration for the fabrication of innovative 3D HA structures with enhanced biological functionality and performance.

A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib.

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 (METex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, METex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1-56.3%], the DCR was 81.3% (95% CI: 63.6-92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6-9.7) and 17.0 month (95% CI: 10.3-not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

Pollutant Emissions and Oxidative Potentials of Particles from the Indoor Burning of Biomass Pellets.

Residential solid fuel combustion significantly impacts air quality and human health. Pelletized biomass fuels are promoted as a cleaner alternative, particularly for those who cannot afford the high costs of gas/electricity, but their emission characteristics and potential effects remain poorly understood. The present laboratory-based study evaluated pollution emissions from pelletized biomass burning, including CH4 (methane), NMHC (nonmethane hydrocarbon compounds), CO, SO2, NOx, PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 µm), OC (organic carbon), EC (element carbon), PAHs (polycyclic aromatic hydrocarbons), EPFRs (environmentally persistent free radicals), and OP (oxidative potential) of PM2.5, and compared with those from raw biomass burning. For most targets, except for SO2 and NOx, the mass-based emission factors for pelletized biomass were 62-96% lower than those for raw biomass. SO2 and NOx levels were negatively correlated with other air pollutants (p < 0.05). Based on real-world daily consumption data, this study estimated that households using pelletized biomass could achieve significant reductions (51-95%) in emissions of CH4, NMHC, CO, PM2.5, OC, EC, PAHs, and EPFRs compared to those using raw biomass, while the differences in emissions of NOx and SO2 were statistically insignificant. The reduction rate of benzo(a)pyrene-equivalent emissions was only 16%, much lower than the reduction in the total PAH mass (78%). This is primarily attributed to the more PAHs with high toxic potentials, such as dibenz(a,h)anthracene, in the pelletized biomass emissions. Consequently, impacts on human health associated with PAHs might be overestimated if only the mass of total PAHs was counted. The OP of particles from the pellet burning was also significantly lower than that from raw biomass by 96%. The results suggested that pelletized biomass could be a transitional substitution option that can significantly improve air quality and mitigate human exposure.

Comprehensive genetic diversity and genome-wide association studies revealed the genetic basis of avocado fruit quality traits.

Introduction: Avocado (Persea americana) is a highly nutritious fruit gaining worldwide popularity. However, its cultivation is currently reliant on a limited number of cultivars with restricted genetic diversity. This study aims to investigate the genetic diversity and population structure of avocado germplasm and identify genetic loci associated with key fruit quality traits that influence customer preference. Methods: A diversity panel of 110 avocado accessions was analyzed using 4,706 high-quality single nucleotide polymorphisms (SNPs). Genetic diversity and population structure were analyzed using pairwise FST, AMOVA, admixture analysis, and phylogenetic analysis. Genome-wide association studies (GWAS) were conducted targeting nine fruit quality traits using two models: General Linear Model (GLM) with Principal Component Analysis (PCA) and Mixed Linear Model (MLM) with PCA and kinship (PCA + K). Results: The analysis revealed three distinct populations corresponding to the three avocado ecotypes: Guatemalan, West Indian, and Mexican. Phylogenetic analysis indicated a closer relationship between the Guatemalan and West Indian races compared to the Mexican race in our Florida germplasm collection. GWAS led to identification of 12 markers within 11 genomic regions significantly associated with fruit quality traits such as fruit color, shape, taste, and skin texture. These markers explained between 14.84% to 43.96% of the phenotypic variance, with an average of 24.63%. Annotation of these genomic regions unveiled candidate genes potentially responsible for controlling these traits. Discussion: The findings enhance our understanding of genetic diversity and population structure in avocado germplasm. The identified genetic loci provide valuable insights into the genetic basis of fruit quality traits, aiding breeding programs in developing improved avocado cultivars. Marker-assisted selection can accelerate the development of new varieties, promoting a more diverse and resilient avocado market.

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing's syndrome.

BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.

An improved SNAP-ADAR tool enables efficient RNA base editing to interfere with post-translational protein modification.

RNA base editing relies on the introduction of adenosine-to-inosine changes into target RNAs in a highly programmable manner in order to repair disease-causing mutations. Here, we propose that RNA base editing could be broadly applied to perturb protein function by removal of regulatory phosphorylation and acetylation sites. We demonstrate the feasibility on more than 70 sites in various signaling proteins and identify key determinants for high editing efficiency and potent down-stream effects. For the JAK/STAT pathway, we demonstrate both, negative and positive regulation. To achieve high editing efficiency over a broad codon scope, we applied an improved version of the SNAP-ADAR tool. The transient nature of RNA base editing enables the comparably fast (hours to days), dose-dependent (thus partial) and reversible manipulation of regulatory sites, which is a key advantage over DNA (base) editing approaches. In summary, PTM interference might become a valuable field of application of RNA base editing.

A machine learning model utilizing delphian lymph node characteristics to predict contralateral central lymph node metastasis in papillary thyroid carcinoma: A prospective multicenter study.

BACKGROUND: This study aimed to use artificial intelligence (AI) to integrate various radiological and clinical pathological data to identify effective predictors of contralateral cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC) and to establish a clinically applicable model to guide the extent of surgery. METHODS: This prospective cohort study included 603 patients with PTC from three centers. Clinical, pathological, and ultrasonographic data were collected and utilized to develop a machine learning (ML) model for predicting CCLNM. Model development at the internal center utilized logistic regression along with other ML algorithms. Diagnostic efficacy was compared among these methods, leading to the adoption of the final model (random forest). This model was subject to AI interpretation and externally validated at other centers. RESULTS: CCLNM was associated with multiple pathological factors. The Delphian lymph node metastasis ratio, ipsilateral cervical lymph node metastasis number, and presence of ipsilateral cervical lymph node metastasis were independent risk factors for CCLNM. Following feature selection, a Delphian lymph node-CCLNM (D-CCLNM) model was established using the Random forest algorithm based on five attributes. The D-CCLNM model demonstrated the highest area under the curve (AUC; 0.9273) in the training cohort and exhibited high predictive accuracy, with AUCs of 0.8907 and 0.9247 in the external and validation cohorts, respectively. CONCLUSIONS: We developed a new, effective method that uses ML to predict CCLNM in patients with PTC. This approach integrates data from Delphian lymph nodes and clinical characteristics, offering a foundation for guiding surgical decisions, and is conveniently applicable in clinical settings.

Enhanced Visible-Light-Driven Photocatalytic Overall Splitting of Pure Water in a Porous Microreactor.

Photocatalytic overall splitting of pure water (H2O) without sacrificial reagent to hydrogen (H2) and oxygen (O2) holds a great potential for achieving carbon neutrality. Herein, by anchoring cobalt sulfide (Co9S8) as cocatalyst and cadmium sulfide (CdS) as light absorber to channel wall of a porous polymer microreactor (PP12), continuous violent H2 and O2 bubbling productions from photocatalytic overall splitting of pure H2O without sacrificial reagent is achieved, with H2 and O2 production rates as high as 4.41 and 2.20 mmol h-1 gcat.-1 respectively. These are significantly enhanced than those in the widely used stirred tank-type reactor in which no O2 is produced and H2 production rate is only 0.004 mmol h-1 gcat.-1. Besides improved charge separation and interaction of H2O with photocatalyst in PP12, bonding interaction of Co9S8 with PP12 creates abundant catalytic active sites for simultaneous productions of H2 and O2, thus leading to the significantly enhanced H2 and O2 bubbling productions in PP12. This offers a new strategy to enhance photocatalytic overall splitting of pure H2O without sacrificial reagent.

Photo-/Electrocatalytic Difunctionalization of Alkenes Enabled by C-H Radical Functionalization.

The difunctionalization of alkenes represents a powerful tool to incorporate two functional groups into the alkene bones for increasing molecular complexity and has been widely utilizations in chemical synthesis. Upon the catalysis of the green, sustainable, mild photo-/electrochemistry technologies, much attentions have been attracted to the development of new tactics for the transformations of the important alkene and alkane feedstocks driven by C-H radical functionalization. Herein, we summarize recent advances in the photo-/electrocatalytic difunctionalization of alkenes enabled by C-H radical functionalization. We detailedly discuss the substrate scope and the mechanisms of the photo-/electrocatalytic alkene difunctionalization reactions by selecting impressive synthetic examples, which are divided into four sections based on the final terminated step, including oxidative radical-polar crossover coupling, reductive radical-polar crossover coupling, radical-radical coupling, and transition-metal-catalyzed coupling.

Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.

Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD.