Evolutionary and ecological forces shape nutrient strategies of mycorrhizal woody plants.

The associations of arbuscular mycorrhizal (AM) or ectomycorrhiza (EcM) fungi with plants have sequentially evolved and significantly contributed to enhancing plant nutrition. Nonetheless, how evolutionary and ecological forces drive nutrient acquisition strategies of AM and EcM woody plants remains poorly understood. Our global analysis of woody species revealed that, over divergence time, AM woody plants evolved faster nitrogen mineralization rates without changes in nitrogen resorption. However, EcM woody plants exhibited an increase in nitrogen mineralization but a decrease in nitrogen resorption, indicating a shift towards a more inorganic nutrient economy. Despite this alteration, when evaluating present-day woody species, AM woody plants still display faster nitrogen mineralization and lower nitrogen resorption than EcM woody plants. This inorganic nutrient economy allows AM woody plants to thrive in warm environments with a faster litter decomposition rate. Our findings indicate that the global pattern of nutrient acquisition strategies in mycorrhizal plants is shaped by the interplay between phylogeny and climate.

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.

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.

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.

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.

The association of post-embryo transfer SARS-CoV-2 infection with early pregnancy outcomes in in vitro fertilization: a prospective cohort study.

BACKGROUND: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies. OBJECTIVE: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. STUDY DESIGN: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m2, undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes. RESULTS: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71). CONCLUSION: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m2. This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer.

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.

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 Mechanical Ventilation Mode Type on Postoperative Pulmonary Complications After Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: It is unknown whether there is a difference in pulmonary outcome in different intraoperative ventilation modes for cardiac surgery with cardiopulmonary bypass (CPB). The aim of this trial was to determine whether patients undergoing cardiac surgery with CPB could benefit from intraoperative optimal ventilation mode. DESIGN: This was a single-center, prospective, randomized controlled trial. SETTING: The study was conducted at a single-center tertiary-care hospital. PARTICIPANTS: A total of 1,364 adults undergoing cardiac surgery with CPB participated in this trial. INTERVENTIONS: Patients were assigned randomly (1:1:1) to receive 1 of 3 ventilation modes: volume-controlled ventilation (VCV), pressure-controlled ventilation (PCV), and pressure-controlled ventilation-volume guaranteed (PCV-VG). All arms of the study received the lung-protective ventilation strategy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of postoperative pulmonary complications (PPCs) within the first 7 postoperative days. Pulmonary complications occurred in 168 of 455 patients (36.9%) in the PCV-VG group, 171 (37.6%) in the PCV group, and 182 (40.1%) in the VCV group, respectively. There was no statistical difference in the risk of overall pulmonary complications among groups (p = 0.585). There were no significant differences in the severity grade of PPCs within 7 days, postoperative ventilation duration, intensive care unit stay, postoperative hospital stay, or 30-day postoperative mortality. CONCLUSIONS: Among patients scheduled for cardiac surgery with CPB, intraoperative ventilation mode type did not affect the risk of postoperative pulmonary complications.

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.

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.

Enzyme-Enabled Droplet Biobattery for Powering Synthetic Tissues.

Enzyme-enabled biobatteries are promising green options to power the next-generation of bioelectronics and implantable medical devices. However, existing power sources based on enzymatic biofuel chemistry exhibit limited scale-down feasibility due to the solid and bulky battery structures. Therefore, miniature and soft alternatives are needed for integration with implants and tissues. Here, a biobattery built from nanolitre droplets, fuelled by the enzyme-enabled oxidation of reduced nicotinamide adenine dinucleotide, generates electrical outputs and powers ion fluxes in droplet networks. Optimization of the droplet biobattery components ensures a stable output current of ~13,000 pA for over 24 h, representing a more than 600-fold increase in output over previous approaches, including light-driven processes. The enzyme-enabled droplet biobattery opens new avenues in bioelectronics and bioiontronics, exemplified by tasks such as the ability to drive electrochemical signal transmission in integrated synthetic tissues.

π-π Interaction-Induced Organic Long-wavelength Room-Temperature Phosphorescence for In Vivo Atherosclerotic Plaque Imaging.

Room-temperature phosphorescent (RTP) materials have great potential for in vivo imaging because they can circumvent the autofluorescence of biological tissues. In this study, a class of organic-doped long-wavelength (≈600 nm) RTP materials with benzo[c][1,2,5] thiadiazole as a guest was constructed. Both host and guest molecules have simple structures and can be directly purchased commercially at a low cost. Owing to the long phosphorescence wavelength of the doping system, it exhibited good tissue penetration (10 mm). Notably, these RTP nanoparticles were successfully used to image atherosclerotic plaques, with a signal-to-background ratio (SBR) of 44.52. This study provides a new approach for constructing inexpensive red organic phosphorescent materials and a new method for imaging cardiovascular diseases using these materials.

Synthesis of Alkylated Polyfluorobenzenes through Decarboxylative Giese Addition of Aliphatic N-Hydroxyphthalimide Esters with Polyfluorostyrene.

Polyfluoroaromatic compounds play crucial roles in medicinal and material science. However, the synthesis of alkylated polyfluoroarenes has been relatively underdeveloped. In this study, we devised a novel decarboxylative coupling reaction between aliphatic N-hydroxyphthalimide esters and polyfluorostyrene, leveraging the photochemical activity of electron donor-acceptor (EDA) complexes. This method offers simple reaction conditions, a broad substrate scope, and excellent functional group tolerance. Furthermore, we have demonstrated the practicality of this protocol through late-stage polyfluoroaryl modification of biologically active molecules using readily available carboxylic acids as starting materials, thus providing an important supplement to the current toolbox for accessing alkylated polyfluoroaryl motifs.

Complete genome sequence of a novel mycovirus from Pleurotus citrinopileatus.

The complete genome sequence of a novel single-stranded [+ ssRNA] positive-sense (+) RNA mycovirus, designated as "Pleurotus citrinopileatus ourmiavirus 1" (PcOV1), isolated from Pleurotus citrinopileatus strain CCMJ2141, was determined. The complete genome of PcOV1 is composed of 2,535 nucleotides. It contains a single open reading frame (ORF), which encodes a protein of 657 amino acids (aa) containing conserved domains of an RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis based on RdRp sequences revealed that PcOV1 is a new member of the genus Ourmiavirus in the family Botourmiaviridae. This is the first virus from P. citrinopileatus to be characterized.

Backbone N-methylation of peptides: Advances in synthesis and applications in pharmaceutical drug development.

Peptide-based drugs have garnered considerable attention in recent years owing to their increasingly crucial role in the treatment of diverse diseases. However, the limited pharmacokinetic properties of peptides have hindered their full potential. One prominent strategy for enhancing the druggability of peptides is N-methylation, which involves the addition of a methyl group to the nitrogen atom of the peptide backbone. This modification significantly improves the stability, bioavailability, receptor binding affinity and selectivity of peptide drug candidates. In this review, we provide a comprehensive overview of the advancements in synthetic methods for N-methylated peptide synthesis, as well as the associated limitations. Moreover, we explore the versatile effects of N-methylation on various aspects of peptide properties. Furthermore, we emphasize the efforts dedicated to N-methylated peptide pharmaceuticals that have successfully obtained marketing approval.

Volatile Versus Total Intravenous Anesthesia on Postoperative Delirium in Adult Patients Undergoing Cardiac Valve Surgery: A Randomized Clinical Trial.

BACKGROUND: The effect of anesthesia regimens on postoperative delirium after on-pump cardiac valve surgery is yet undetermined. This study aimed to evaluate the effect of volatile anesthesia compared with propofol-based total intravenous anesthesia (TIVA) on the occurrence of delirium after on-pump cardiac valve surgery. METHODS: This randomized clinical trial was conducted at a university academic hospital in China, from February 2019 to January 2021. Patients scheduled for on-pump cardiac valve surgery or combined valve with coronary artery bypass grafting (CABG) surgeries were randomly assigned to receive anesthesia maintenance with either a volatile anesthetic (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was the incidence of delirium during the first 7 days after surgery, assessed using the confusion assessment method for the intensive care unit (ICU). The secondary outcomes included duration of delirium, subtypes of delirium, 30-day mortality, pain score, major morbidity (including cerebral infarction, respiratory failure, and pneumonia), duration of mechanical ventilation, and lengths of ICU and hospital stay. The statistical analysis of the primary outcome variable was by Pearson's χ 2 test. RESULTS: Among the 684 patients analyzed (mean age, 53.8 years; 381 [55.7%] women), 676 were assessed for the primary outcome. Postoperative delirium occurred in 63 of 337 (18.7%) patients receiving volatile anesthesia versus 76 of 339 (22.4%) patients receiving propofol-based TIVA (relative risk, 0.80; 95% confidence interval [CI], 0.55-1.16; P = .231). There were no significant differences between the groups in any of the secondary outcomes. CONCLUSIONS: Among patients undergoing on-pump cardiac valve surgery, anesthesia maintenance with a volatile agent did not result in significantly fewer occurrences of postoperative delirium than propofol-based TIVA.

Improved Self-Heating in Short-Channel Monolayer WS2 Transistors with High-Thermal Conductivity BeO Dielectrics.

Two-dimensional semiconducting transition metal dichalcogenides (TMDs) enable ultimate channel length scaling of transistor technology due to their atomic-thin body nature, which also brings the challenge of a pronounced self-heating effect inside the ultrathin channel. In particular, high current density under high electric field could lead to negative differential resistance behavior due to self-heating, not only limiting the current carrying capability of the TMDs transistors but also leading to severe reliability issues. Here, we report high-performance monolayer WS2 transistors on a high-thermal-conductivity BeO dielectric with effective suppression of the self-heating effects, eliminating the negative differential resistance behavior at high field, as observed in the case of the HfO2 dielectric. The monolayer CVD WS2 device on BeO with a 50 nm channel length exhibits a record-high on-state current of 325 µA/µm, transconductance (gm) of 150 µS/µm, and a on/off ratio of 1.8 × 108 at Vds = 1 V, far exceeding previous results.

ICI plus chemotherapy prolonged survival over ICI alone in patients with previously treated advanced NSCLC.

OBJECTIVES: Immune checkpoint inhibitors (ICI) monotherapy was standard of care in second-line treatment of patients with advance non-small cell lung cancer (NSCLC). This study aims to investigate the efficacy of ICI plus chemotherapy in patients with previously treated advanced NSCLC. PATIENTS AND METHODS: An investigator-initiated trial (IIT) aiming to evaluate the efficacy and safety of ICI in combination with chemotherapy as second line and beyond for patients with advanced NSCLC was undergone at Shanghai Pulmonary Hospital (ChiCTR1900026203). Patients who received ICI monotherapy as second or later line setting during the same period were also collected as a comparator. RESULTS: From April 2018 to June 2019, 31 patients were included into this IIT study, simultaneously 51 patients treated with ICI monotherapy were selected as a comparator. ICI plus chemotherapy showed a significantly higher ORR (35.5% vs. 15.7%, p=0.039), prolonged PFS (median: 5.6 vs. 2.5 months, p = 0.013) and OS (median: NE vs. 12.6 months, p = 0.038) compared with ICI alone. In the subgroup of negative PD-L1 expression (9 patients in combination group and 12 patients in monotherapy group), ICI plus chemotherapy also had a favorable ORR (44.4% vs. 8.3%, p = 0.119), longer PFS (median: 6.5 vs 3.0 months, p < 0.05) and OS (median: NE vs. 8.2 months, p = 0.117). Meanwhile, the addition of chemotherapy did not increase immune-related adverse events. CONCLUSIONS: ICI plus chemotherapy showed superior ORR, PFS and OS than ICI alone patients with previous treated advanced NSCLC. These findings warrant further investigation.