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Covalent organic frameworks (COFs) are an emerging class of crystalline organic materials that have shown potential to be a new physical platform. In this work, a designed COF named AB-COF, which has novel enantiomorphic Kagome bands, is proposed and a feasible route to synthesize it is given. Via a combination of first-principles calculations and tight-binding analysis, we investigate the electronic structures and the phase interference of the COF. It becomes topologically nontrivial when doping one iodine atom in a unit cell. The Berry curvatures of the valence band (VB) and conduction band (CB) of the iodine-doped AB-COF show opposite values and different distributions. This provides an opportunity to study the new mechanism of circular dichroism from the different Berry curvatures of the VB and CB. Surprisingly, the circular-dichroism dissymmetry factor of AB-COF reaches a theoretical maximum value, and the oscillator strength data are in agreement with this result. When two iodine atoms are doped in a unit cell, the Berry curvatures of the VB and CB also have different values, but with more symmetry and similar distributions. This behavior enhances the circular dichroism with a wider range of dissymmetric absorption, and the circular dichroism dissymmetry factor also reaches its theoretical maximum value. [ABSTRACT FROM AUTHOR]

Searching for multiferroic materials with ferromagnetic (FM) and ferroelectric (FE) properties holds promise for ultra‐high‐density and low‐energy‐consumption memory device applications, but 2D materials with both properties are rare. Herein, a general strategy to achieve nonvolatile electric field control of magnetism in the bilayer (BL) α‐In2Se3 by hole doping is proposed. By first‐principles calculations, it is demonstrated that hole doping can induce robust ferromagnetism in the bilayer α‐In2Se3 due to its unique flat Mexican‐hat‐shape valence band structure. Such band edges cause van Hove singularities (VHS), and proper hole doping can lead to time‐reversal symmetry breaking. The bilayer α‐In2Se3 exhibits ferromagnetism and ferroelectricity within a wide range of doping concentrations, resulting in an unexpected multiferroic phase. Furthermore, when the electrical polarization of α‐In2Se3 flips from downward to upward, it becomes non‐magnetic (NM) from ferromagnetic states in the As‐substituted bilayer α‐In2Se3, which can work as a nonvolatile magnetic storage unit. Remarkably, the As‐substituted bilayer α‐In2Se3 exhibits an enhanced magnetic moment of 1.2 μB per AsSe due to substantial charge transfer across the interface. Notably, the mechanism of electrically controlled magnetism is elucidated as the coupling among the Mexican‐hat‐like dispersion, ferromagnetism, and ferroelectricity. The findings offer a promising strategy for electrical writing and the magnetic reading memory device. [ABSTRACT FROM AUTHOR]

Green manufacture of steroid precursors from diosgenin by microbial replacing multistep chemical synthesis has been elusive. It is currently limited by the lack of strain and degradation mechanisms. Here, we demonstrated the feasibility of this process using a novel strain Mycolicibacterium sp. HK‐90 with efficiency in diosgenin degradation. Diosgenin degradation by strain HK‐90 involves the selective removal of 5,6‐spiroketal structure, followed by the oxygenolytic cleavage of steroid nuclei. Bioinformatic analyses revealed the presence of two complete steroid catabolic gene clusters, SCG‐1 and SCG‐2, in the genome of strain HK‐90. SCG‐1 cluster was found to be involved in classic phytosterols or cholesterol catabolic pathway through the deletion of key kstD1 gene, which promoted the mutant m‐∆kstD1 converting phytosterols to intermediate 9α‐hydroxyandrostenedione (9‐OHAD). Most impressively, global transcriptomics and characterization of key genes suggested SCG‐2 as a potential gene cluster encoding diosgenin degradation. The gene inactivation of kstD2 in SCG‐2 resulted in the conversion of diosgenin to 9‐OHAD and 9,16‐dihydroxy‐pregn‐4‐ene‐3,20‐dione (9,16‐(OH)2‐PG) in mutant m‐ΔkstD2. Moreover, the engineered strain mHust‐ΔkstD1,2,3 with a triple deletion of kstDs was constructed, which can stably accumulate 9‐OHAD by metabolizing phytosterols, and accumulate 9‐OHAD and 9,16‐(OH)2‐PG from diosgenin. Diosgenin catabolism in strain mHust‐ΔkstD1,2,3 was revealed as a progression through diosgenone, 9,16‐(OH)2‐PG, and 9‐OHAD to 9α‐hydroxytestosterone (9‐OHTS). So far, this work is the first report on genetically engineered strain metabolizing diosgenin to produce 21‐carbon and 19‐carbon steroids. This study presents a promising biosynthetic platform for the green production of steroid precursors, and provide insights into the complex biochemical mechanism of diosgenin catabolism. [ABSTRACT FROM AUTHOR]

The kagome lattice is one of the most intriguing topics to study. It has a frustrated flat band touching a set of Dirac bands and can possess various promising properties, such as ferromagnetism, superconductivity, and a non-trivial topology. Covalent organic frameworks (COFs) are a rare type of inorganic material, however, they can provide a platform for generating certain required lattices. Based on first-principles density functional theory calculations, we show that a newly synthesized two-dimensional COF named COF-SH has novel enantiomorphic kagome bands, which include two sets of flat bands touching the Dirac bands around the Fermi level. The Bloch wave of the flat-valence band at the K-point shows the kagome nature of the phase interference. Under charge doping, the COF-SH exhibits a ferromagnetic ground state. Moreover, when COF-SH is doped with iodine atoms, a sizable gap in the system is opened between the flat bands and the Dirac bands due to the spin–orbit coupling (SOC) effect. Meanwhile, the spin degeneracy is lifted since the organic layer loses electrons due to the oxidizing property of iodine. In addition, our tight-binding analysis with the SOC effect shows that the flat valence band separates from the Dirac bands and holds a nonzero Chern number. Consequently, this I-doped COF can give rise to a quantum anomalous Hall effect. [ABSTRACT FROM AUTHOR]

Background: The survival benefit from later-line treatment for patients with metastatic colorectal cancer (mCRC) remains disappointing. Here, in a real-world study, we were aimed to evaluate which choice will affect the survival of mCRC patients after standard treatment in Chinese patients. Methods: A total of 129 patients with refractory mCRC were involved in the study. They received targeted monotherapy or combined with chemo-agents or PD-1 inhibitor before death. Overall survival (OS) and progression-free survival (PFS) were reviewed and evaluated from clinical features and treatment options. Results: Among the 129 patients, the median age was 56 years (25–81). The mOS from third-line was 12.5 months. OS of patients who treated with chemo plus targeted therapy group in third-line was shown to be superior to pd-1 inhibitor in combination with antiangiogenic agents or antiangiogenic monotherapy group (15.6 m vs. 10.5 m vs. 8.4 m, p < 0.05). Patients had received triplet-drugs (bevacizumab plus low-dose irinotecan and oxaliplatin) and had prolonged survival compared to those had not (21.3 m vs 10.3 m, p = 0.004). OS between patients who had immunotherapy history or not was not significantly different (p > 0.05). The mPFS was 3.5 months in patients who had administered with antiangiogenic targeted agents plus anti-pd-1 and 4.7 months in chemo plus targeted therapy group and 2.2 months in the other group. In the triplet drugs group, preliminary results showed that ORR was 13.3% and DCR was 80%. The median PFS was 5.1 m, and the median OS was 10.6 m. Conclusions: Triplet drugs resulted in significantly longer overall survival, and immunotherapy may have limited benefit in MSS type CRC patients. [ABSTRACT FROM AUTHOR]

In this study, we compared two anomalous wet February periods in 2021 and 2022 in China. The same anomalies appeared in the spatial distribution of precipitation, with anomalous precipitation centered over the southeast coast. However, temperature discrepancies appeared in most of China, with anomalously high temperatures in 2021 and lower temperatures in 2022. Both instances of increased precipitation were attributed to warm and moist advection from the south, with transport in 2021 being partly enhanced by the South China Sea cyclone, whereas transport in 2022 was mainly due to the subtropical western North Pacific anticyclone. Therefore, in this study, we aimed to compare and analyze temperature and precipitation anomalies in February 2021 and 2022 using the self-organizing map method. Warm events in East Asia and cold events in Siberia and the Tibetan Plateau types were obtained by mode 1, which contained 2021. Mode 6 exhibited opposite warm types in Siberia and cold types in southern Asia, including February temperature and precipitation anomalies in 2022. Based on the results of this study, we can conclude that precipitation anomalies in February 2021 and 2022 occurred under different temperature and circulation anomalies, and both were influenced by La Niña events. Autumn sea ice loss in the Barents Sea contributed significantly to warm and rainy events in February 2021. However, the cold and rainy events of February 2022 were closely related to the strengthening of the Siberian High. [ABSTRACT FROM AUTHOR]

Janus MoSSe with mirror asymmetry has recently emerged as a new two-dimensional (2D) material with a sizeable out-of-plane dipole moment. Here, based on first-principles calculations, we theoretically investigate the electronic properties of two patterns of 2D MoSSe/MoS2 van der Waals heterostructures (vdWHs). The electronic properties of MoSSe can be tuned by the intrinsic out-of-plane dipole field. When the Se side of the Janus layer faces the MoS2 layer, the dipole field points from the MoSSe layer towards the MoS2 layer, and the vdWH possesses a type-I band alignment which is desirable for light emission applications. With a reversal of the Janus layer, the intrinsic field inverts accordingly, and the band alignment becomes a typical type-II band alignment, which benefits carrier separation. Moreover, it possesses superior optical absorption (∼105 cm−1), and the calculated photocurrent density under visible-light radiation is up to 0.9 mA cm−2 in the MoSSe/MoS2 vdWH. Meanwhile, an external electric field and vertical strain can remarkably modulate the band alignment to switch it between type-I and type-II. Thus, MoSSe/MoS2 vdWHs have promising applications in next-generation photovoltaic devices. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths in the world and often diagnosed at an advanced stage, so it is urgent to explore the pathogenesis and new diagnostic biomarkers. Accumulated evidences suggested that small nucleolar RNAs (snoRNAs) played a key role in the development and progression of NSCLC. To examine differential expression snoRNA profile and identify snoRNAs with clinical significance in lung adenocarcinoma (LUAD), The Cancer Genome Atlas (TCGA) LUAD RNA sequencing dataset was used to investigate differential expression snoRNA signatures and compared with snoRNA PCR array analysis in pair-matched LUAD tissues. The diagnostic ability of SONRD60 was assessed using a receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to plot survival curves. Univariate and multivariate Cox regression analyses were used to investigate the prognostic effect of SNORD60 expression on LUAD. The results showed that SNORD60 was a significantly upregulated snoRNA after intersection analysis in LUAD cases. SNORD60 has 74.2% sensitivity and 75.3% specificity for the diagnosis of LUAD. Increased SNORD60 expression was linked with lymph node metastases and the TNM stage (P < 0.05). Pathological T category and lymph node metastases were independent prognostic factors for overall survival in a multivariate Cox regression study. Our findings demonstrated that SNORD60, a small nucleolar RNA, has an oncogenic function in LUAD and might be used as a new early diagnostic biomarker for LUAD. [ABSTRACT FROM AUTHOR]

Background: In our previous phase II study, nab-paclitaxel plus S-1 (NPS) showed encouraging objective response rate (ORR) as first-line treatment for advanced pancreatic adenocarcinoma (APAC). This study aimed to evaluate the effectiveness and safety of S-1 maintenance after NPS in APAC and to explore factors predicting survival benefits when using S-1 maintenance. Methods: Between 2014 and 2018 a total of 182 patients with APAC, who were primarily treated with NPS, were included. For patients without progression or with treatment discontinuation due to any reasons within 4 months during NPS treatment, S-1 monotherapy was administrable as maintenance therapy at the physicians' discretion based on the patients' preference and performance status. Efficacy and safety of S-1 maintenance were investigated. Results: In 123 patients without progression within 4 months during NPS treatment, 74 received S-1 maintenance and had median progression-free survival of 9.6 months and median overall survival of 16.7 months. Multivariable analysis showed that in patients receiving S-1 maintenance after first-line NPS therapy, an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, non-metastatic disease, and complete or partial response as best response to NPS chemotherapy were independently associated with better survival. The most common all-grade hematological and non-hematological adverse events were neutropenia (82.4%) and peripheral neurotoxicity (66.2%), respectively, and the most common ≥Grade 3 hematological and non-hematological adverse events were neutropenia (40.5%) and peripheral neurotoxicity (6.8%), respectively in patients who received S-1 maintenance. Conclusions: Our real-world study showed that S-1 maintenance after tumor response or stable disease induced by first-line NPS treatment was effective and well-tolerated for some patients with APAC, which offers a promising alternative treatment strategy with encouraging survival for APAC. [ABSTRACT FROM AUTHOR]

Background: The highly heterogeneous characteristics of GC may limit the accuracy of a single biomarker for screening populations benefiting from immunotherapy. However, the combination of multiple indicators can provide more directed information for the detection of potential immune benefit subgroups. At present, there are no recognized complex indexes to identify advanced GC (AGC) in patients who likely benefited from immunotherapy. The objective of this research is to explore whether the composite biomarker of derived neutrophil–lymphocyte ratio (dNLR) and platelet–lymphocyte ratio (PLR) can be used as a reliable prognostic factor for the survival of AGC patients receiving immunotherapy. Methods: From December 2014 to May 2021, a total 238 AGC patients at a single Center were included in this retrospective cohort research study. The cutoff value of dNLR was obtained by the ROC curves to predict the disease progression rate at the 8th month and the cutoff value of PLR was estimated by the median value. The cutoff values of dNLR and PLR were 1.95 and 163.63, respectively. The high levels of dNLR (≥1.95) and PLR (≥163.63) were considered to be risk factors. Based on these two risk factors, patients were categorized into 3 groups: the risk factor number for the "good" group was 0, that for the "intermediate" group was 1, and that for the "poor" group was 2. The subjects were divided into two groups: dNLR/PLR-good and dNLR/PLR-intermediate/poor. Results: Of the 238 patients, the median overall survival (mOS) and progression-free survival (mPFS) were 12.5 and 4.7 months, respectively. Multivariate analysis revealed that the good dNLR/PLR group was independently associated with better prognosis. The intermediate/poor dNLR/PLR group was independently correlated with an over 1.4 times greater risk of disease progression (4.1 months vs. 5.5 months; p = 0.016) and an over 1.54 times greater risk of death (11.1 months vs. 26.3 months; p = 0.033) than the good dNLR/PLR group. However, no clear differences in the disease control rate (DCR) and overall response rate (ORR) were observed between the intermediate/poor dNLR/PLR group and the good dNLR/PLR group (51.5% vs. 56.3%, 26.3% vs. 29.6%; p = 0.494, p = 0.609). Conclusion: Our study firstly verifies that the composite biomarker of dNLR and PLR is an independent prognostic factor affecting survival of advanced AGC patients receiving immunotherapy. It may be difficult for patients with the intermediate/poor dNLR/PLR group to benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Background and Aims: Biomarkers for systemic inflammation have been introduced into clinical practice for risk-rating in cancer patients' treatment. This study is aimed at confirming the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) as an effective biomarker for patients with metastatic gastric cancer (MGC) receiving anti-PD-1 agents.Method: Patients with MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and November 2020 were reviewed. The study analyzed the association of NLR and overall survival (OS) or progression-free survival (PFS) and antitumor response rate with PD-1 inhibitors.Results: 137 patients were included in the final analysis. The area under the curve value of NLR for 6-month OS was 0.71. The best cut-off value for NLR was 3.23. NLR < 3.23 was associated with longer OS (HR = 0.38, 95% CI, 0.26-0.57, p < 0.001) and PFS (HR = 0.42, 95% CI, 0.29-0.62, p < 0.001) in patients with MGC. No significant difference was observed in the objective response rate (ORR) (35.8% vs. 28.6%, p = 0.377) and disease control rate (DCR) (86.4% vs. 78.6%, p = 0.229) in the NLR < 3.23 group and in the NLR ≥ 3.23 group, respectively. Univariate analysis and multivariate analysis found that NLR was an independent prognosis biomarker for PFS and OS.Conclusions: Pretreatment elevated NLR was significantly associated with inferior PFS and OS in patients with MGC who received anti-PD-1 inhibitors. Clinicians need to consider patients with elevated NLR for decisions on immunotherapy strategy. [ABSTRACT FROM AUTHOR]

Background: There are limited treatment options for advanced biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer. We compared the efficacy and safety of PD-1 inhibitors plus chemotherapy and chemotherapy alone as first-line treatment in patients with advanced BTC. Methods: We retrospectively reviewed patients with BTC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor with chemotherapy (anti-PD-1+C group) or chemotherapy alone (C group). Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) was analyzed using Kaplan–Meier survival curves with log-rank tests. Objective response rate (ORR), disease control rate (DCR), and safety were also analyzed. Results: This study included 75 patients who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) plus chemotherapy and 59 patients who received chemotherapy alone. After matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 5.8m in the anti-PD-1+C group, which was significantly longer than the C group, at 3.2m (HR: 0.47, 95% CI 0.29 to 0.76, P = 0.004). The ORR was 21.7% and DCR was 80.4% in the anti-PD-1+C group, while the ORR was 15.2% and DCR was 69.6% in the C group. No significant differences were found in the ORR and DCR between the two groups (P=0.423, P=0.231). Grade 3 or 4 treatment was related to adverse events (AEs) that occurred in the anti-PD-1+C group, namely hypothyroidism (n=3, 6.5%), rash (n=2, 4.2%), and hepatitis (n=1, 2.2%). There was no AE-related death. The grade 3-4 leukopenia rate was similar in the two groups (4.3% vs. 6.5%). Conclusions: Anti-PD-1 therapy plus chemotherapy prolonged the PFS compared with chemotherapy alone in advanced BTC with controllable AEs. Further clinical trials are needed to confirm this result. [ABSTRACT FROM AUTHOR]

Background: Biomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC. Methods: We retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level. Results: We included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001). Conclusions: Our study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding. [ABSTRACT FROM AUTHOR]

A novel streptomyces trypsin GM2938 was selected as the object of study. The active GM2938 contains 223 amino acid residues. Constructing recombinant plasmid and transforming Bacillus subtilis SCK6, the heterogenous expression of GM2938 was achieved. Through optimization of fermentation conditions, the expression level of GM2938 reached 1622.2 U/mL (esterase activity) and 33.8 U/mL (amidase activity). The recombinant trypsin was purified and measured: the specific activity of esterase was 5.6 × 103 U/mg, and the specific activity of amidase was 1.1 × 103 U/mg. Furthermore, the enzymatic properties of GM2938 were explore: the optimal reaction temperature and pH were 50 °C and 9.0, respectively; the recombinant enzyme show high stability at 25 °C and range of pH 5.0–9.0; Ca2+, K+, Mg2+, EDTA, DTT, DMSO, methanol, glycerin and ethanediol could promote the esterase and amidase activities at the investigated concentrations, while Fe2+, SDS, tritonx-100, acetone, chloroform and n-hexane inhibited the trypsin activities. Kinetic parameters of GM2938 were calculated: the K m of BAEE was 3.15 × 10−5 mol·L−1, Vmax value was 2.87 × 10−4 mol·L−1·min−1; the K m of BAPAN was 2.20 × 10−4 mol·L−1, the Vmax was 2.40 × 10−4 mol·L−1·min−1. These properties give trypsin GM2938 a potential application prospect. [ABSTRACT FROM AUTHOR]

Abstract Recently, several studies showed that microcystin-LR (MCLR) can accumulate and induce toxicity in kidney. However, the exact mechanism is unknown. The aim of this study was to explore the mechanism of MCLR-induced nephrotoxicity. To this end, adult zebrafish were exposed to MCLR (0, 1, 5 and 25 μg/L) for 60 days. Exposure to MCLR caused histopathological lesions, which were characterized by renal tubules filled with eosinophilic casts, abnormal renal tubules, intertubular space decrease, and blood infiltration in renal cells. RNA-Seq analysis indicated that exposure to MCLR significantly interfered with renal gene expressions, and these genes were enriched in various pathways, such as oxidative phosphorylation, cell cycle, and protein processing in endoplasmic reticulum, which were related to apoptosis. Furthermore, terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR exposure induced renal cell apoptosis. In addition, negative changes of the reactive oxygen species (ROS) level as well as apoptotic-related gene, protein expressions and enzyme activities suggested that MCLR could induce production of ROS, subsequently triggering apoptosis via p53-bcl-2 and caspase-dependent pathway in the kidney of zebrafish. Therefore, it can be concluded that apoptosis is a primary case of MCLR-induced nephrotoxicity. Highlights • MCLR exposure can trigger histopathological lesions in renal tissue of adult zebrafish. • TUNEL assay reveals MCLR exposure could cause apoptosis in zebrafish kidney. • P53-bcl-2 and caspase-dependent apoptosis pathway contribute greatly to MCLR-induced renal apoptosis. [ABSTRACT FROM AUTHOR]

A novel ultrafast and low-loss lateral injection-enhanced gate transistor (LIEGT) is proposed and investigated by simulation. The device features a MOS-controlled shorted anode (MCSA) and a bias voltage (${V}_{{AG}}$) applied between the anode trench gate (ATG) and the anode electrode. The n+ anode is shorted to the N-buffer through the MOS channel around the ATG when the MCSA is activated with ${V}_{{AG}} > {V}_{{th}}$ during turn-off and blocking states, and thus the p+ anode/N-buffer junction is unactivated. The MCSA LIEGT turns off as fast as a unipolar device by optimizing the time gap to activate the MCSA before turning off the cathode trench gate (CTG). The activated MCSA would deactivate hole injection from the anode side and synchronously quickly extract the electrons from the N-drift, which improves the switching speed and dramatically decreases the turn-off energy loss (${E}_{ \mathrm{\scriptscriptstyle OFF}}$). In the blocking state, the MCSA LIEGT achieves a MOS breakdown mode instead of an open base p-n-p bipolar breakdown mode. Thus, the breakdown voltage (BV) is not only improved but also independent of the p+ anode doping concentration. In the forward conduction state with ${V}_{{AG}} = {0}$ , the MCSA is unactivated and hence the MCSA LIEGT operates like a conventional LIEGT without deteriorating the on-state voltage drop (${V}_{ \mathrm{\scriptscriptstyle ON}}$). Compared with the conventional LIEGT, the proposed device decreases ${E}_{ \mathrm{\scriptscriptstyle OFF}}$ by 88% and improves the BV by 13% at the same ${V}_{ \mathrm{\scriptscriptstyle ON}}$. Importantly, ${E}_{ \mathrm{\scriptscriptstyle OFF}}$ is almost independent of ${V}_{ \mathrm{\scriptscriptstyle ON}}$. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common types of cancer worldwide, with the highest mortality rate of all types of cancer. In the present study, epidermal growth factor receptor (EGFR) mutations of 354 primary patients with non-small cell lung cancer (NSCLC) of Chinese ethnicity were detected following formalin-fixed and paraffin-embedded specimen DNA extraction, polymerase chain reaction amplification, and sanger sequencing. The total rate of occurrence of EGFR somatic mutation in these 354 patients was 48.02%. Of these detected EGFR mutations, 27.40% were located in exon 19 and 25.99% in exon 21. The most frequent mutation in exon 19 was E746-A750del (8.47%), and in exon 21, L858R (10.17%). EGFR mutation rates were significantly associated with sex [female vs. male: 60.13 vs. 38.81%; adjusted odds ratio (OR), 1.93, 95% confidence interval (CI), 1.07-3.51, P=0.029], age (<60 vs. =60; 58.62 vs. 40.67%; adjusted OR, 1.87; 95% CI, 1.20-2.92; P=0.006) and histology [adenocarcinoma (ADC) vs. non-ADC; 52.76 vs. 26.56%; adjusted OR, 2.35; 95% CI, 1.28-4.50; P=0.007]. The frequency of E746_A750del, Q787Q and L858R mutations were significantly different in ADC patients compared with squamous cell carcinoma patients (P<0.001). Furthermore, a novel EGFR mutation, M793K, was detected in 7 NSCLC patients with possible gefitinib resistance. The present study analyzed the EGFR exon 18-21 mutation occurrence profile for Chinese patients with NSCLC and identified significant associations between different EGFR mutations with demographic and histological factors. These results may offer clinical benefits and potential novel treatments. [ABSTRACT FROM AUTHOR]

The enrichment of CD20+ and CD138+ immune cells were previously associated with improved survival in colorectal cancer (CRC). We previously discovered that the resected tumors in CRC patients were highly enriched with interleukin (IL)-10-producing CD19loCD27hi plasmablasts with potential suppressor functions. It is still unknown what roles the CD19loCD27hi plasmablasts play in CRC patients. In this study, we first demonstrated that B cells from peripheral blood mononuclear cells (PBMCs) could be stimulated to resemble tumor-infiltrating plasmablasts using a coculture containing Caco-2 and heat-killed bacteria. The PBMC-derived CD19loCD27hi plasmablasts and tumor-infiltrating plasmablasts contained comparable frequencies of IL-10-expressing cells and secreted similar levels of IL-10. We later found that these CD19loCD27hi plasmablasts significantly suppressed the mRNA and cytokine expression of IL-17A in PBMCs, as well as the expression of RAR-related orphan receptor gamma t (RORγt) in CD4+ T cells. This suppressive effect did not involve the induction of Foxp3+ regulatory T cells, since no upregulation of Foxp3 level was observed. Through IL-10/IL-10R blocking and exogenous IL-10 experiments, we found that these CD19loCD27hi plasmablasts primarily mediated IL-17A suppression through IL-10 production. Other B cell-related mechanisms might also contribute to this inhibitory effect. In our cohort of patients, patients with high frequency of tumor-infiltrating IL-10+ CD19loCD27hi plasmablasts presented low IL-17A+ CD4+ T cell frequency and better survival. Altogether, these results suggested that CD19loCD27hi plasmablasts with Breg functions were associated with better prognosis in CRC, possibly by suppressing harmful Th17 inflammation. [ABSTRACT FROM AUTHOR]

Nonsmall cell lung cancer (NSCLC) is greatly affected by the dysregulation of the immune system. Circulating follicular helper T cells (Tfh) play critical roles in inducing B-cell activation and producing various cytokines. In the current study, we investigated levels of circulating Tfh in NSCLC. Circulating Tfh and it subtypes were determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 in 62 NSCLC patients and 66 healthy controls using flow cytometry. Data presented that percentage of circulating Tfh in the peripheral CD4+ T cells was significantly increased in NSCLC (14.0%) than in controls (8.7%) ( p<0.001). Further analysis revealed that the upregulation of Tfh was contributed by the Th2-Tfh subtype and the Th17-Tfh subtype, whereas the percentage of the Th1-Tfh subtype was significantly decreased in patients. Investigating the clinical stages of the patients demonstrated that prevalence of Tfh was significantly elevated in cases with advanced stages (III: 14.2%; IV: 16.4%) than those with primary stages (I: 10.9%; II: 10.8%). In addition, we analyzed Tfh in patients with different histological types. Results showed that the percentage of circulating Tfh was further upregulated in adenocarcima than squamous cell carcinoma or other types. This study suggests the involvement of circulating Tfh in the pathogenesis and progression of NSCLC, and provides a potential pathway for understanding this disease. [ABSTRACT FROM AUTHOR]

Inflammation plays a critical role in the initiation of colorectal cancer but is also required to mediate antitumor immunity in established tumors. Therefore, identifying the cellular and molecular components in colorectal tumors is necessary for the understanding of tumor progression and the development of novel treatment strategies. In this study, we demonstrated that a specific subtype of regulatory B cells, the CD19 lo CD27 hi plasmablasts, was enriched in the colorectal tumor microenvironment. This CD19 lo CD27 hi plasmablast subset presented high interleukin 10 (IL-10) expression but not transforming growth factor-β (TGF-β) secretion. Phenotypically, the tumor-infiltrating IL-10 + CD19 lo CD27 hi plasmablasts presented lower CD24, CD38, and IgA, and higher Tim-1 and IgG expression compared to the IL-10 − CD19 lo CD27 hi plasmablasts. The tumor-infiltrating IL-10 + CD19 lo CD27 hi plasmablasts were found to be gut-homing due to their higher expression of α4β7 while peripheral blood B cells did not show the same characteristic. When cocultured with autologous T cells, CD19 lo CD27 hi plasmablasts demonstrated potent activity in suppressing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) expression but did not promote Foxp3 expression. Overall, this study demonstrate that in colorectal cancer, CD19 lo CD27 hi plasmablasts make up a large percentage in tumor-infiltrating lymphocytes and possess potent immunoregulatory functions, and thus could be utilized in future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: The survival benefit from later-line treatment for patients with metastatic colorectal cancer (mCRC) remains disappointing. Here, in a real-world study, we were aimed to evaluate which choice will affect the survival of mCRC patients after standard treatment in Chinese patients., Methods: A total of 129 patients with refractory mCRC were involved in the study. They received targeted monotherapy or combined with chemo-agents or PD-1 inhibitor before death. Overall survival (OS) and progression-free survival (PFS) were reviewed and evaluated from clinical features and treatment options., Results: Among the 129 patients, the median age was 56 years (25-81). The mOS from third-line was 12.5 months. OS of patients who treated with chemo plus targeted therapy group in third-line was shown to be superior to pd-1 inhibitor in combination with antiangiogenic agents or antiangiogenic monotherapy group (15.6 m vs. 10.5 m vs. 8.4 m, p < 0.05). Patients had received triplet-drugs (bevacizumab plus low-dose irinotecan and oxaliplatin) and had prolonged survival compared to those had not (21.3 m vs 10.3 m, p = 0.004). OS between patients who had immunotherapy history or not was not significantly different (p > 0.05). The mPFS was 3.5 months in patients who had administered with antiangiogenic targeted agents plus anti-pd-1 and 4.7 months in chemo plus targeted therapy group and 2.2 months in the other group. In the triplet drugs group, preliminary results showed that ORR was 13.3% and DCR was 80%. The median PFS was 5.1 m, and the median OS was 10.6 m., Conclusions: Triplet drugs resulted in significantly longer overall survival, and immunotherapy may have limited benefit in MSS type CRC patients., Competing Interests: Declarations Consent for Publication All the authors had consent for publication. Ethics Approval and Consent to Participate This retrospective study was approved by the independent ethics committee of the Chinese PLA General Hospital and performed in accordance with the Declaration of Helsinki, and all the authors obtained written informed consent from the participants, to participate in the study. Competing Interests The authors declare no competing interests., (© 2024. The Author(s).)

Abstract: Post-operative bile leakage (POBL) is a serious complication following hepatobiliary surgery, with potentially life-threatening consequences if left untreated. This article presents a successful case of POBL management without surgical intervention. A 31-year-old male, diagnosed with bile leakage before hospitalisation, underwent percutaneous biliary drainage (PTBD) to address bilomas. Follow-up after 3 months indicated biloma atrophy and POBL healing but revealed bile duct stenosis. The patient received a larger biliary drainage tube, and after 1 month, the biloma and tube were removed. A 1-year follow-up confirmed the patient's excellent health. This case underscores the safety and efficacy of PTBD for managing POBL, offering a non-invasive alternative for patients with this complication. PTBD presents a viable treatment option for POBL cases, minimising the need for surgical interventions and their associated risks., (Copyright © 2024 Copyright: © 2024 Journal of Minimal Access Surgery.)

Background: Metastatic gastric cancer (MGC) patients with progression on first-line treatment still have poor outcomes on chemotherapy. The KEYNOTE-061 study demonstrated that pembrolizumab, a PD-1inhibitor, was not better than paclitaxel as second-line therapy for MGC. Herein, we explored the efficacy and safety of PD-1inhibitor based treatment for MGC patients in the second line., Methods: In this observational, retrospective study, we enrolled MGC patients treated with anti-PD-1 based therapy as second-line in our hospital. We primarily assessed the treatment's efficacy and safety. We also evaluated the relationship between clinical features and outcomes using univariate and multivariate analyses., Results: We enrolled 129 patients with an objective response rate (ORR) of 16.3% and a disease control rate (DCR) of 79.1%. Patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents had ORR of 19.6% and higher DCR of 94.1%. The median progression-free survival (PFS) was 4.10 months, and the median overall survival (OS) was 7.60 months. In univariate analysis, patients treated with PD-1inhibitor combined with chemotherapy and anti-angiogenic agents and with prior anti-PD-1 history were significantly associated with favorable PFS and OS. In the multivariate analysis, different combination therapy and prior anti-PD-1 history were independent prognosis biomarkers for PFS and OS. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 28 (21.7%) patients. Common adverse events (AEs) included fatigue, hyper/hypothyroidism, neutrophil decrease, anemia, skin reactions, proteinuria, and hypertension. We did not observe treatment-related deaths., Conclusion: Our current results indicated that PD-1-inhibitor and chemo-anti-angiogenic agents combination therapy and prior PD-1 treatment history might improve clinical activity for GC immunotherapy as second-line treatment with acceptable safety profiles. Further studies are needed to verify those outcomes for MGC in other centers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gou, Zhang, Wang and Dai.)

Background: Lung immune prognostic index (LIPI), a combination of derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH), is currently attracting considerable interest as a potential prognostic indicator in many malignancies. Our study aimed to investigate the prognostic value of preoperative LIPI in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing radical resection., Methods: We retrospectively reviewed PDAC patients treated with radical resection from February 2019 to April 2021 at Chinese People's Liberation Army (PLA) general hospital. Based on the cut-off value of dNLR and LDH identified by X-tile, patients were divided into LIPI good and LIPI intermediate/poor group. Kaplan-Meier curve and log-rank test were used to compare the recurrence-free survival (RFS) and overall survival (OS) of the two groups. Univariate and multivariate Cox regression was used to identify the independent prognostic value of LIPI. Subgroup analysis was performed to identify specific population benefited from radical resection., Results: A total of 205 patients were included and the median RFS and OS was 10.8 and 24.3 months, respectively. Preoperative LIPI intermediate/poor was related to worse RFS and OS ( p  < 0.05). Preoperative LIPI intermediate/poor, vascular invasion and no adjuvant chemotherapy were indicators of poor OS. Patients with LIPI intermediate/poor had worse OS especially among females and those with adjuvant chemotherapy ( p  < 0.05). Adjuvant chemotherapy related to better RFS and OS in patients with LIPI good ( p  < 0.05)., Conclusions: Preoperative LIPI intermediate/poor can be an indicator of poor prognosis in patients with PDAC undergoing radical resection. LIPI good could be an effective marker of benefit from adjuvant chemotherapy. Larger studies are warranted for further validation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhou, Deng, Wang and Dai.)

Janus MoSSe with mirror asymmetry has recently emerged as a new two-dimensional (2D) material with a sizeable out-of-plane dipole moment. Here, based on first-principles calculations, we theoretically investigate the electronic properties of two patterns of 2D MoSSe/MoS 2 van der Waals heterostructures (vdWHs). The electronic properties of MoSSe can be tuned by the intrinsic out-of-plane dipole field. When the Se side of the Janus layer faces the MoS 2 layer, the dipole field points from the MoSSe layer towards the MoS 2 layer, and the vdWH possesses a type-I band alignment which is desirable for light emission applications. With a reversal of the Janus layer, the intrinsic field inverts accordingly, and the band alignment becomes a typical type-II band alignment, which benefits carrier separation. Moreover, it possesses superior optical absorption (∼10 5 cm -1 ), and the calculated photocurrent density under visible-light radiation is up to 0.9 mA cm -2 in the MoSSe/MoS 2 vdWH. Meanwhile, an external electric field and vertical strain can remarkably modulate the band alignment to switch it between type-I and type-II. Thus, MoSSe/MoS 2 vdWHs have promising applications in next-generation photovoltaic devices.

Background: Immunotherapy has shown promising results for metastatic gastric cancer (MGC) patients. Nevertheless, not all patients can benefit from anti-PD-1 treatment. Thus, this study aimed to develop and validate a prognostic nomogram for MGC patients that received immunotherapy., Methods: Herein, MGC patients treated with anti-PD-1 between 1 October 2016 and 1 June 2022 at two separate Chinese PLA General Hospital centers were enrolled and randomly divided into training and validation sets (186 and 80 patients, respectively). The nomogram was constructed based on a multivariable Cox model using baseline variables from the training cohort. Its predictive accuracy was validated by the validation set. The consistency index (C-index) and calibration plots were used to evaluate the discriminative ability and accuracy of the nomogram. The net benefit of the nomogram was evaluated using decision curve analysis (DCA). Finally, we stratified patients by median total nomogram scores and performed Kaplan-Meier survival analyses., Results: We developed the nomogram based on the multivariate analysis of the training cohort, including four parameters: surgery history, treatment line, lung immune prognostic index (LIPI), and platelet-to-lymphocyte ratio (PLR). The C-index of the nomogram was 0.745 in the training set. The calibration curve for 1- and 2-year survival showed good agreement between nomogram predictions and actual observations. In the validation group, the calibration curves demonstrated good performance of the nomogram, with a C-index for overall survival (OS) prediction of 0.713. The OS of patients with a score greater than the median nomogram score was significantly longer than patients with a score lower or equal to the median ( p < 0.001)., Conclusion: We constructed a nomogram to predict the outcomes of MGC patients that received immunotherapy. This nomogram might facilitate individualized survival predictions and be helpful during clinical decision-making for MGC patients under anti-PD-1 therapy., Competing Interests: Author LW and QF were employed by the company Genetron Health (Beijing) Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gou, Qian, Zhang, Wei, Fan, Wang and Dai.)

Background: Fruquintinib, a vascular endothelial growth factor receptor inhibitor, is a new anticancer drug independently developed in China to treat refractory metastatic colorectal cancer (mCRC). In Japan, regorafenib combined with nivolumab has been demonstrated to be promising in patients with refractory mCRC. Here, in a real-world study, we were aimed to evaluate the efficacy of fruquintinib with various programmed death-1 (PD-1) inhibitors after standard treatment in Chinese non-microsatellite instability-high (MSI-H)/mismatch repair proficient mCRC patients., Methods: A total of 45 patients with refractory mCRC were involved in the study. They received fruquintinib (3 or 5 mg, orally administered once a day for 3 weeks followed by 1 week off in 4-week cycles) and a PD-1 inhibitor(200 mg pembrolizumab, 3 mg/kg nivolumab, 200 mg sintilimab or camrelizumab, intravenously administered on D1 once every 3 weeks). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and objective response rate (ORR) were reviewed and evaluated., Results: Among the 45 patients, the median age was 54 years (29-85). The ORR was 11.1% (5/45), DCR 62.2% (28/45), median PFS equal 3.8 months, and median OS was 14.9 months. The response duration was 3.4 months. PFS between left and right primary tumors and PFS with or without lung metastases were both not significantly different ( p > 0.05), which was inconsistent with the result of REGONIVO study. The multivariate analysis indicated no association of OS benefit in the specified subgroups. No adverse-effect-related deaths were reported., Conclusions: Fruquintinib, in combination with anti-PD-1, was observed to have clinical activity in a small population of patients with heavily pretreated mCRC in our center. Further studies are needed to verify this outcome in a large population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gou, Qian, Zhang, Yan, Si, Wang and Dai.)

A novel Gram-stain-positive, coccoid or short rod-shaped, moderate-orange-pigmented, halotolerant and psychrotolerant bacterium, designated strain SCU63 T , was isolated from a saline soil sample in China, and characterized by a polyphasic taxonomic approach. 16S rRNA gene sequence similarity of strain SCU63 T to species in the genera Planococcus and Planomicrobium ranged from 96.5 to 98.6 %. Phylogenetic trees as well as diagnostic signature nucleotides in the 16S rRNA gene sequence supported the view that this strain should be assigned to the genus Planococcus. Further, average nucleotide identity and digital DNA-DNA hybridization analyses confirmed the separate species status of strain SCU63 T relative to the closely related taxa. The isolate grew at 0-40 °C (optimum, 30-35 °C), at pH 6.5-9.0 (pH 7.0-7.5) and in the presence of 0-15 % (w/v) NaCl (3 %). The principal fatty acids were anteiso-C15 : 0, C16 : 1ω7c alcohol, iso-C16 : 0 and iso-C14 : 0, and the dominant isoprenoid quinones were MK-8 and MK-7. The peptidoglycan type was determined to be A4α (l-Lys-d-Glu), and the polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminophospholipid and one unidentified lipid. The DNA G+C content was 44.6 mol%. Based on the genotypic, phenotypic and chemotaxonomic data, strain SCU63 T can be classified as a novel species in the genus Planococcus, for which the name Planococcushalotolerans sp. nov. is proposed. The type strain is SCU63 T (=CGMCC 1.13628 T =KCTC 43001 T ).