PMS2 amplification contributes brain metastasis from lung cancer.

BACKGROUND: Lung adenocarcinoma metastasizing to the brain results in a notable increase in patient mortality. The high incidence and its impact on survival presents a critical unmet need to develop an improved understanding of its mechanisms. METHODS: To identify genes that drive brain metastasis of tumor cells, we collected cerebrospinal fluid samples and paired plasma samples from 114 lung adenocarcinoma patients with brain metastasis and performed 168 panel-targeted gene sequencing. We examined the biological behavior of PMS2 (PMS1 Homolog 2)-amplified lung cancer cell lines through wound healing assays and migration assays. In vivo imaging techniques are used to detect fluorescent signals that colonize the mouse brain. RNA sequencing was used to compare differentially expressed genes between PMS2 amplification and wild-type lung cancer cell lines. RESULTS: We discovered that PMS2 amplification was a plausible candidate driver of brain metastasis. Via in vivo and in vitro assays, we validated that PMS2 amplified PC-9 and LLC lung cancer cells had strong migration and invasion capabilities. The functional pathway of PMS2 amplification of lung cancer cells is mainly enriched in thiamine, butanoate, glutathione metabolism. CONCLUSION: Tumor cells elevated expression of PMS2 possess the capacity to augment the metastatic potential of lung cancer and establish colonies within the brain through metabolism pathways.

Impact of the comprehensive remediation project on hydrological conditions in the lower reaches of the Ganjiang River.

This study undertakes a systematic analysis of the hydrological changes before and after the implementation of the Comprehensive Remediation Project in the lower reaches of the Ganjiang River. It focuses on changes in downstream inflow, ratios of flow distribution, and water levels, as well as water velocity near the gates. The results indicate a significant improvement in the spatial distribution of water resources in the lower reaches of the Ganjiang River. The project enhances the inflow from the northern and southern branches, positively influencing downstream water usage and the ecological environment. Building upon these findings, the study proposes operational recommendations tailored to different hydrological years, such as timely adjustments to the southern branch's water inflow and optimizing flow distribution ratios. This research provides a scientific basis for the implementation and dispatch of comprehensive remediation projects and offers insights into water resource management in similar regions.

Association between mechanical power during one-lung ventilation and pulmonary complications after thoracoscopic lung resection surgery: a prospective observational study.

BACKGROUND: The role of mechanical power on pulmonary outcomes after thoracic surgery with one-lung ventilation was unclear. We investigated the association between mechanical power and postoperative pulmonary complications in patients undergoing thoracoscopic lung resection surgery. METHODS: In this single-center, prospective observational study, 622 patients scheduled for thoracoscopic lung resection surgery were included. Volume control mode with lung protective ventilation strategies were implemented in all participants. The primary endpoint was a composite of postoperative pulmonary complications during hospital stay. Multivariable logistic regression models were used to evaluate the association between mechanical power and outcomes. RESULTS: The incidence of pulmonary complications after surgery during hospital stay was 24.6% (150 of 609 patients). The multivariable analysis showed that there was no link between mechanical power and postoperative pulmonary complications. CONCLUSIONS: In patients undergoing thoracoscopic lung resection with standardized lung-protective ventilation, no association was found between mechanical power and postoperative pulmonary complications. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058528, date of registration: April 10, 2022.

Effect of corneal cross-linking on biomechanical changes following transepithelial photorefractive keratectomy and femtosecond laser-assisted LASIK.

Purpose: To evaluate the change in corneal biomechanics in patients with postoperative ectasia risk when combining two common laser vision correction procedures (tPRK and FS-LASIK) with cross-linking (in tPRK Xtra and FS-LASIK Xtra). Methods: The study included 143 eyes of 143 myopic, astigmatic patients that were divided into non-cross-linked refractive surgery groups (non-Xtra groups, tPRK and FS-LASIK) and cross-linked groups (Xtra groups, tPRK Xtra and FS-LASIK Xtra) according to an ectasia risk scoring system. The eyes were subjected to measurements including the stress-strain index (SSI), the stiffness parameter at first applanation (SP-A1), the integrated inverse radius (IIR), the deformation amplitude at apex (DA), and the ratio of deformation amplitude between apex and 2 mm from apex (DARatio2mm). The measurements were taken preoperatively and at 1, 3, and 6 months postoperatively (pos1m, pos3m, and pos6m). Posterior demarcation line depth from the endothelium (PDLD) and from the ablation surface (DLA) were recorded at pos1m. Results: SP-A1 significantly decreased, while IIR, deformation amplitude, and DARatio2mm increased significantly postoperatively in all four groups (p < 0.01)-all denoting stiffness decreases. In the FS-LASIK group, the changes in IIR, DA, and DARatio2mm were 32.7 ± 15.1%, 12.9 ± 7.1%, and 27.2 ± 12.0% respectively, which were significantly higher (p < 0.05) compared to 20.1 ± 12.8%, 6.4 ± 8.2%, and 19.7 ± 10.4% in the FS-LASIK Xtra group. In the tPRK group, the change in IIR was 27.3 ± 15.5%, significantly larger than 16.9 ± 13.4% in the tPRK Xtra group. The changes of SSI were minimal in the tPRK (-1.5 ± 21.7%, p = 1.000), tPRK Xtra (8.4 ± 17.9%, p = 0.053), and FS-LASIK Xtra (5.6 ± 12.7%, p = 0.634) groups, but was significant in the FS-LASIK group (-12.1 ± 7.9%, p < 0.01). After correcting for baseline biomechanical metrics, preoperative bIOP and the change in central corneal thickness (△CCT) from pre to pos6m, the changes in the IIR in both FS-LASIK and tPRK groups, as well as DA, DARatio2mm and SSI in the FS-LASIK group remained statistically greater than their corresponding Xtra groups (all p < 0.05). Most importantly, after correcting for these covariates, the changes in DARatio2mm in the FS-LASIK Xtra became statistically smaller than in the tPRK Xtra (p = 0.017). Conclusion: The statistical analysis results indicate that tPRK Xtra and FS-LASIK Xtra effectively reduced the biomechanical losses caused by refractive surgery (tPRK and FS-LASIK). The decrease in corneal overall stiffness was greater in FS-LASIK than in tPRK, and the biomechanical enhancement of CXL was also higher following LASIK than after tPRK.

Pathological progression of osteoarthritis: a perspective on subchondral bone.

Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.

Halogen-Bond-Promoted Direct Cross-Coupling of Trifluoromethylated Alkyl Bromides with Coumarins/Quinolinones: Unraveling Trifluoromethyl Effects.

This study introduces a novel approach involving XB-mediated cross-coupling of α-trifluoromethylated alkyl bromides with coumarins and quinolinones under visible light irradiation. Both density functional theory (DFT) calculations and experimental studies converge to suggest that the noncovalent interaction between alkyl bromides and DMAP, intensified by the α-trifluoromethyl group, plays a pivotal role in facilitating this chemoselective reaction.

Effects of deep brain stimulation on dopamine D2 receptor binding in patients with treatment-refractory depression.

BACKGROUND: Depression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. METHODS: Six patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BPND) with the cerebellum as reference tissue. RESULTS: Depression and anxiety symptoms improved after 3-6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BPND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). LIMITATIONS: This study was limited to the small sample size and lack of a healthy control group. CONCLUSIONS: Chronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system.

Clinical efficacy of acupuncture therapy combined with core muscle exercises in treating patients with chronic nonspecific low back pain: a systematic review and meta-analysis of randomized controlled trials.

Introduction: This meta-analysis aimed to determine the clinical efficacy of acupuncture combined with core muscle exercises on pain and functional status in patients with chronic nonspecific low back pain. Methods: This study followed the Preferred Reporting Items for Systematic Reviews and meta-analysis criteria for systematic reviews and meta-analyses. Randomized controlled trials published till November 2023 were searched in PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang databases. The search strategy was related to disease type, intervention, and control measures and was structured around the search terms "low back pain," "acupuncture therapy," and "exercise." Two reviewers applied inclusion and exclusion criteria. Sensitivity and fixed effects analyses were performed to determine the primary outcomes. Results: We included 11 randomized controlled trials (n = 727) on acupuncture combined with core muscle exercises in patients with chronic nonspecific low back pain. Compared with controls, clinical efficacy was significant, with improvements in pain scores (visual analog pain scale and numerical rating scale) and Oswestry Disability Index in the intervention group. Discussion: Acupuncture therapy combined with core muscle exercises improved pain and functional status in patients with chronic nonspecific low back pain, with favorable clinical outcomes compared with single-core muscle training. Multicenter large-sample trials are required to obtain more reliable conclusions.

Osimertinib in combination with anti-angiogenesis therapy presents a promising option for osimertinib-resistant non-small cell lung cancer.

BACKGROUND: Osimertinib has become standard care for epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients whereas drug resistance remains inevitable. Now we recognize that the interactions between the tumor and the tumor microenvironment (TME) also account for drug resistance. Therefore, we provide a new sight into post-osimertinib management, focusing on the alteration of TME. METHODS: We conducted a retrospective study on the prognosis of different treatments after osimertinib resistance. Next, we carried out in vivo experiment to validate our findings using a humanized mouse model. Furthermore, we performed single-cell transcriptome sequencing (scRNA-seq) of tumor tissue from the above treatment groups to explore the mechanisms of TME changes. RESULTS: Totally 111 advanced NSCLC patients have been enrolled in the retrospective study. The median PFS was 9.84 months (95% CI 7.0-12.6 months) in the osimertinib plus anti-angiogenesis group, significantly longer than chemotherapy (P = 0.012) and osimertinib (P = 0.003). The median OS was 16.79 months (95% CI 14.97-18.61 months) in the osimertinib plus anti-angiogenesis group, significantly better than chemotherapy (P = 0.026), the chemotherapy plus osimertinib (P = 0.021), and the chemotherapy plus immunotherapy (P = 0.006). The efficacy of osimertinib plus anlotinib in the osimertinib-resistant engraft tumors (R-O+A) group was significantly more potent than the osimertinib (R-O) group (P<0.05) in vitro. The combinational therapy could significantly increase the infiltration of CD4+ T cells (P<0.05), CD25+CD4+ T cells (P<0.001), and PD-1+CD8+ T cells (P<0.05) compared to osimertinib. ScRNA-seq demonstrated that the number of CD8+ T and proliferation T cells increased, and TAM.mo was downregulated in the R-O+A group compared to the R-O group. Subtype study of T cells explained that the changes caused by combination treatment were mainly related to cytotoxic T cells. Subtype study of macrophages showed that proportion and functional changes in IL-1ß.mo and CCL18.mo might be responsible for rescue osimertinib resistance by combination therapy. CONCLUSIONS: In conclusion, osimertinib plus anlotinib could improve the prognosis of patients with a progressed disease on second-line osimertinib treatment, which may ascribe to increased T cell infiltration and TAM remodeling via VEGF-VEGFR blockage.

Strategies to alleviate distortive phase transformations in Li-ion intercalation reactions: an example with vanadium pentoxide.

Chemical and electrochemical Li-ion insertion in transition metal oxides, either via a phase transformation reaction (ions insert into specific crystallographic sites of the host lattice) or a solid solution insertion (ions distribute uniformly throughout the host lattice), enables high energy density electrochemical energy storage. Many phase transformation cathode materials, that undergo two-phase reactions, exhibit high theoretical capacities arising from multi-electron redox reactions. However, challenges in distortive phase transformations and uncontrolled phase nucleation, propagation, segregation, and co-existence continue to limit the energy density, (dis)charging rate performances, and cycling stability of available phase transformation cathode materials. Vanadium pentoxide (V2O5), a classical layered intercalation host material with high theoretical capacity, undergoes irreversible structural changes and capacity fading when intercalating more than one lithium ion per V2O5 unit in its thermodynamically stable phase. Here, we review recent synthetic strategies to alter the V-O connectivity, thereby alleviating distortive phase transformations and promoting solid solution-based Li-ion insertion in V2O5. We also summarize several widely accessible and classical molecular-based analytical tools that can provide local structural dynamics and phase transformation mechanism information on the lithiation of V2O5, including single-crystal X-ray diffraction, infrared and Raman spectroscopy, electron paramagnetic resonance, and nuclear magnetic resonance spectroscopy.

Multiple evidence reveals two new species and new distributions of Calocybe species (Lyophyllaceae) from northeastern China.

The Calocybe species possess notable economic and medicinal value, demonstrating substantial potential for resource utilization. The taxonomic studies of Calocybe are lacking in quality and depth. Based on the specimens collected from northeast China, this study provides a detailed description of two newly discovered species, namely Calocybebetulicola and Calocybecystidiosa, as well as two commonly found species, Calocybedecolorata and Calocybeionides. Additionally, a previously unrecorded species, C.decolorata, has recently been discovered in Jilin Province, China. The two newly discovered species can be accurately distinguished from other species within the genus Calocybe based on their distinct morphological characteristics. The primary distinguishing features of C.betulicola include its grayish-purple pileus, grayish-brown to dark purple stipe, smaller basidiomata, absence of cellular pileipellis, and its habitat on leaf litter within birch forests. Calocybecystidiosa is distinguished by its growth on the leaf litter of coniferous forests, a flesh-pink pileus, a fibrous stipe with a white tomentose covering at the base, non-cellular pileipellis, larger basidiospores, and the presence of cheilocystidia. The reconstruction of phylogenetic trees using combined ITS, nLSU, and tef1-α sequences, employing maximum likelihood and Bayesian inference analyses, showed that C.betulicola formed a cluster with C.decurrens, while C.cystidiosa clustered with C.vinacea. However, these two clusters formed separate branches themselves, which also supported the results obtained from our morphological studies. A key to the Calocybe species reported from northeast China is provided to facilitate future studies of the genus.

Enzymatic Hydrolysis Optimization of Yak Whey Protein Concentrates and Bioactivity Evaluation of the Ultrafiltered Peptide Fractions.

Yak whey protein concentrates (YWPCs) have good functional properties, but there is still a gap in the study of their peptides. In this study, peptides were obtained by enzymatic hydrolysis, and the bioactivity of each ultrafiltration fraction was evaluated using an optimal process. YWPCs were isolated and purified from yak milk as the raw material. Alkaline protease, trypsin, and papain were used to hydrolyze YWPCs. The protease with the highest degree of hydrolysis (DH) and peptide concentration was selected as the most suitable enzyme. The effects of pH, temperature, time, and the enzyme-to-substrate ratio (E/S) on the DH and peptide concentration were investigated, and response surface methodology was utilized to optimize the hydrolysis process. The hydrolysate was separated using ultrafiltration membranes with molecular weight cut-offs of 10 kDa, 5 kDa, 3 kDa, and 1 kDa. The bioactivity of each ultrafiltration component was analyzed, including the inhibition rates of α-amylase and xanthine oxidase (XOD) activities and the scavenging rates of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radicals. The results indicated that alkaline protease was the best enzyme for hydrolyzing YWPCs. The peptide concentration in the YWPC hydrolysate was the highest (17.21 mg/mL) at a pH of 8 and a concentration of 7500 U/g, after 2.5 h at 62 °C. The enzymatic hydrolysate was ultrafiltered to yield four peptide fractions, of which the <1 kDa peptides exhibited the highest α-amylase inhibitory activity (22.06%), XOD inhibitory activity (17.15%), and ABTS cationic free radical scavenging rate (69.55%). This demonstrates the potential of YWPC hydrolyzed peptides for hypoglycemic, uric acid-lowering, and antioxidant applications, providing a theoretical basis for the high-value utilization of YWPCs.

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders.

BACKGROUND: Chronic liver diseases constitute a major global public health burden, posing a substantial threat to patients' daily lives and even survival due to the potential development of musculoskeletal disorders. Although the relationship between chronic liver diseases and musculoskeletal disorders has received extensive attention, their causal relationship has not been comprehensively and systematically investigated. METHODS: This study aimed to assess the causal relationships between viral hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC), liver cirrhosis, and hepatocellular carcinoma (HCC) with osteoporosis, osteoarthritis, and sarcopenia through bidirectional Mendelian randomization (MR) research. The traits related to osteoporosis and osteoarthritis included both overall and site-specific phenotypes, and the traits linked to sarcopenia involved indicators of muscle mass and function. Random-effect inverse-variance weighted (IVW), weighted median, MR-Egger, and Causal Analysis Using the Summary Effect Estimates were used to evaluate causal effects, with IVW being the main analysis method. To enhance robustness, sensitivity analyses were performed using Cochran's Q test, MR-Egger intercept, MR-PRESSO global test, funnel plots, leave-one-out analyses, and latent causal variable model. RESULTS: The forward MR analysis indicated that PSC can reduce forearm bone mineral density (beta = - 0.0454, 95% CI - 0.0798 to - 0.0110; P = 0.0098) and increase the risk of overall osteoarthritis (OR = 1.012, 95% CI 1.002-1.022; P = 0.0247), while HCC can decrease grip strength (beta = - 0.0053, 95% CI - 0.008 to - 0.0025; P = 0.0002). The reverse MR analysis did not find significant causal effects of musculoskeletal disorders on chronic liver diseases. Additionally, no heterogeneity or pleiotropy was detected. CONCLUSIONS: These findings corroborate the causal effects of PSC on osteoporosis and osteoarthritis, as well as the causal impact of HCC on sarcopenia. Thus, the implementation of comprehensive preventive measures is imperative for PSC and HCC patients to mitigate the risk of musculoskeletal disorders, ultimately improving their quality of life.

Comprehensive analysis of clinicopathological profiles in adenosquamous carcinoma of the lung.

OBJECTIVES: Adenosquamous carcinoma (ASC), an uncommon subtype within non-small cell lung cancer (NSCLC), manifests distinctive traits of aggressiveness, embodying a fusion of both adenocarcinoma (AC) and squamous cell carcinoma (SCC) components. The clinicopathological characteristics of distinct subtypes of ASC remain unclear. METHODS: This retrospective study included 226 patients diagnosed with lung ASC who consecutively underwent surgical resection at Shanghai Pulmonary Hospital, Tongji University, between January 2015 and March 2021. Data regarding the clinical features and pathological features were collected. RESULTS: Out of this study cohort, 125 patients exhibited AC-predominant ASC, while 81 had SCC-predominant ASC. No significant differences were observed between the two subgroups in terms of age, gender, smoking history, primary site, and T, N classification. AC-Predominant ASC displayed a higher susceptibility to genetic alterations compared to SCC-Predominant ASC (P=0.02). Additionally, we showed that irrespective of the predominant pathological subtype in ASC, when lymph node metastasis occurred, the lymph node biopsies were more likely to exhibit AC, and a chi-square test confirmed that the primary predominant pathological subtype was not associated with the lymph node metastasis subtype. CONCLUSIONS: In conclusion, we describe an overview of ASC in the Chinese population, and upon stratifying into predominant pathological subgroups, we observed a higher frequency of driver gene mutations in AC-predominant ASC. We found that the AC component in ASC has a higher propensity for lymph node metastasis. These findings may suggest the predominant role of the AC component within the context of ASC.

Migration-Enhanced Epitaxial Growth of InAs/GaAs Short-Period Superlattices for THz Generation.

The low-temperature-grown InGaAs (LT-InGaAs) photoconductive antenna has received great attention for the development of highly compact and integrated cheap THz sources. However, the performance of the LT-InGaAs photoconductive antenna is limited by its low resistivity and mobility. The generated radiated power is much weaker compared to the low-temperature-grown GaAs-based photoconductive antennas. This is mainly caused by the low abundance of excess As in LT-InGaAs with the conventional growth mode, which inevitably gives rise to the formation of As precipitate and alloy scattering after annealing. In this paper, the migration-enhanced molecular beam epitaxy technique is developed to grow high-quality (InAs)m/(GaAs)n short-period superlattices with a sharp interface instead of InGaAs on InP substrate. The improved electron mobility and resistivity at room temperature (RT) are found to be 843 cm2/(V·s) and 1648 ohm/sq, respectively, for the (InAs)m/(GaAs)n short-period superlattice. The band-edge photo-excited carrier lifetime is determined to be ~1.2 ps at RT. The calculated photocurrent intensity, obtained by solving the Maxwell wave equation and the coupled drift-diffusion/Poisson equation using the finite element method, is in good agreement with previously reported results. This work may provide a new approach for the material growth towards high-performance THz photoconductive antennas with high radiation power.

Cross-regulation between proteome reallocation and metabolic flux redistribution governs bacterial growth transition kinetics.

Bacteria need to adjust their metabolism and protein synthesis simultaneously to adapt to changing nutrient conditions. It's still a grand challenge to predict how cells coordinate such adaptation due to the cross-regulation between the metabolic fluxes and the protein synthesis. Here we developed a dynamic Constrained Allocation Flux Balance Analysis method (dCAFBA), which integrates flux-controlled proteome allocation and protein limited flux balance analysis. This framework can predict the redistribution dynamics of metabolic fluxes without requiring detailed enzyme parameters. We reveal that during nutrient up-shifts, the calculated metabolic fluxes change in agreement with experimental measurements of enzyme protein dynamics. During nutrient down-shifts, we uncover a switch of metabolic bottleneck from carbon uptake proteins to metabolic enzymes, which disrupts the coordination between metabolic flux and their enzyme abundance. Our method provides a quantitative framework to investigate cellular metabolism under varying environments and reveals insights into bacterial adaptation strategies.

In-depth proteomic analysis identifies key gene signatures predicting therapeutic efficacy of anti-PD-1/PD-L1 monotherapy in non-small cell lung cancer.

Background: Immunotherapy has opened up a new era of individualized treatment for non-small cell lung cancer (NSCLC) with negative driver gene mutations. Anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies have been the main options for immunotherapy over the past decade. Screening for predictive markers of anti-PD-1/PD-L1-responsive patients remains a focus in the field of immunotherapy, especially on the protein level in which relevant proteomic biomarkers are still lacking. Methods: We collected samples from 23 patients with NSCLC who received anti-PD-1/PD-L1 monotherapy and were followed up for three years. The proteomic profile of the tumor was obtained by mass spectrometry (MS). Meanwhile, we combined the RNA sequencing (RNA-seq) data of 27 patients treated with anti-PD-1/PD-L1 therapy in a previous study to establish an integrated gene network. Weighted correlation network analysis (WGCNA) and elastic network were implemented to screen the top gene modules for predicting treatment-responsive patients. Gene expression related mutational patterns were also retrieved for validation in the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort. Results: Our results showed the gene expression profile of MOXD1, PHAF1, KRT7, ANKRD30A, TMEM184A, KIR3DL1, and KCNK4 could better predict the durable response to anti-PD-1/PD-L1 therapy, with the specificity and sensitivity of 0.76 and 0.6, respectively. Besides, the mutational gene profile associated with these genes also suggested an association with favorable response in the MSKCC cohort. Patient-specific protein-protein interaction (PPI) network also indicated strong correlation among KRT7, TMEM184A and ANKRD30A. Conclusions: Our study indicated that key gene signatures identified by machine learning model could be utilized for clinical screening of patients who might benefit from anti-PD-1 therapy. Further mechanistic investigations around these genes are warranted.

Daily life affective dynamics as transdiagnostic predictors of mental health symptoms: An ecological momentary assessment study.

BACKGROUND: Affective dynamics have been identified as a correlate of a broad span of mental health issues, making them key candidate transdiagnostic factors. However, there remains a lack of knowledge about which aspects of affective dynamics - especially as they manifest in the course of daily life - relate to a general risk for mental health issues versus specific symptoms. METHODS: We leverage an ecological momentary assessment (EMA) study design with four measures per day over a two-week period to explore how negative affect levels, inertia, lability, and reactivity to provocation and stress in the course of daily life relate to mental health symptoms in young adults (n = 256) in the domains of anxiety, depression, psychosis-like symptoms, behaviour problems, suicidality, and substance use. RESULTS: Dynamic structural equation modelling (DSEM) suggested that negative affect levels in daily life were associated with depression, anxiety, indirect and proactive aggression, psychosis, anxiety, and self-injury; negative affective lability was associated with depression, physical aggression, reactive aggression, suicidal ideation, and ADHD symptoms; negative affective inertia was associated with depression, anxiety, physical aggression, and cannabis use; and emotional reactivity to provocation was related to physical aggression. LIMITATIONS: The cross-sectional design, the limited span of mental health issues included, and the convenience nature and small size of the sample are limitations. CONCLUSIONS: Findings suggest that a subset of mental health symptoms have shared negative affective dynamics patterns. Longitudinal research is needed to rigorously examine the directionality of the effects underlying the association between affective dynamics and mental health issues.

Catalyst-free decarboxylative cross-coupling of N-hydroxyphthalimide esters with tert-butyl 2-(trifluoromethyl)acrylate and its application.

Here, we demonstrate a practical method toward the facile synthesis of CF3-containing amino acids through visible light promoted decarboxylative cross-coupling of a redox-active ester with tert-butyl 2-(trifluoromethyl)acrylate. The reaction was driven by the photochemical activity of electron donor-acceptor (EDA) complexes that were formed by the non-covalent interaction between a Hantzsch ester and a redox-active ester. The advantages of this protocol are its synthetic simplicity, rich functional group tolerance, and a cost-effective reaction system.

Effect of Volatile Anesthesia Versus Intravenous Anesthesia on Postoperative Pulmonary Complications in Patients Undergoing Minimally Invasive Esophagectomy: A Randomized Clinical Trial.

BACKGROUND: The effect of intraoperative anesthetic regimen on pulmonary outcome after minimally invasive esophagectomy for esophageal cancer is yet undetermined. The aim of this study was to determine the effect of volatile anesthesia (sevoflurane or desflurane) compared with propofol-based intravenous anesthesia on pulmonary complications after minimally invasive esophagectomy. METHODS: Patients scheduled for minimally invasive esophagectomy were randomly assigned to 1 of 3 general anesthetic regimens (sevoflurane, desflurane, or propofol). The primary outcome was the incidence of pulmonary complications within the 7 days postoperatively, which was a collapsed composite end point, including respiratory infection, pleural effusion, pneumothorax, atelectasis, respiratory failure, bronchospasm, pulmonary embolism, and aspiration pneumonitis. The severity of pulmonary complications, surgery-related complications, and other secondary outcomes were also assessed. RESULTS: Of 647 patients assessed for eligibility, 558 were randomized, and 553 were analyzed. A total of 185 patients were assigned to the sevoflurane group, 185 in the desflurane, and 183 in the propofol group. Patients receiving a volatile anesthetic (sevoflurane or desflurane) had a significantly lower incidence (36.5% vs 47.5%; odds ratio, 0.63; 95% confidence interval, 0.44-0.91; P = .013) and lower severity grade of pulmonary complications (P = .035) compared to the patients receiving propofol. There were no statistically significant differences in other secondary outcomes between the 2 groups. CONCLUSIONS: In patients undergoing minimally invasive esophagectomy, the use of volatile anesthesia (sevoflurane or desflurane) resulted in the reduced risk and severity of pulmonary complications within the first 7 postoperative days as compared to propofol-based intravenous anesthesia.