Gold-Catalyzed Diyne-Ene Annulation for the Synthesis of Polysubstituted Benzenes through Formal [3+3] Approach with Amide as the Critical Co-Catalyst.

The one-step synthesis of tetra-substituted benzenes was accomplished via gold-catalyzed diyne-ene annulation. Distinguished from prior modification methods, this novel strategy undergoes formal [3+3] cyclization, producing polysubstituted benzenes with exceptional efficiency.  The critical factor enabling this transformation was the introduction of amides, which were reported for the first time in gold catalysis as covalent nucleophilic co-catalysts.  This interesting protocol not only offers a new strategy to achieve functional benzenes with high efficiency, but also enlightens potential new reaction pathways within gold-catalyzed alkyne activation processes.

Elevating Discharge Voltage of Li2CO3-routine Li-CO2 Battery over 2.9 V at an Ultra-wide Temperature Window.

The Li-CO2 batteries utilizing greenhouse gas CO2 possess advantages of high energy density and environmental friendliness. However, these batteries following Li2CO3-product route typically exhibit low work voltage (<2.5 V) and energy efficiency. Herein, we have demonstrated for the first time that cobalt phthalocyanine (CoPc) as homogeneous catalyst can elevate the work plateau towards 2.98 V, which is higher than its theoretical discharge voltage without changing the Li2CO3-product route. This unprecedented discharge voltage is illustrated by mass spectrum and electrochemical analyses that CoPc has powerful adsorption capability with CO2 (-7.484 kJ/mol) and forms discharge intermediate of C33H16CoN8O2. Besides high discharge capacity of 18724 mAh/g and robust cyclability over 1600 hours (1000 mAh/g cut-off) at a current density of 100 mA/g , the batteries show high temperature adaptability (-30~80 °C). Our work is paving a promising avenue for the progress of high-efficiency Li-CO2 batteries.

Association between daily sitting time and kidney stones based on the National Health and Nutrition Examination Survey (NHANES) 2007-2016: A cross-sectional study.

BACKGROUND: Kidney stones are among the most common urological conditions affecting approximately 9% of the world population. Although some unhealthy diets and unhealthy lifestyles are reportedly risk factors for kidney stone, the association between daily sitting time and kidney stone has not been explored. MATERIALS AND METHODS: This large-scale, cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) database 2007-2016. Kidney stone history and daily sitting time were retrieved from the questionnaire and 24-hour recall interviews. Logistic regression and subgroup analysis were conducted to investigate the association. The analysis was further stratified by vigorous recreational activity. RESULTS: A total of 19188 participants aged ≥20 years with complete information were included in this study. The overall prevalence of kidney stone was 9.6%. Among participants without vigorous recreational activity, a trend towards an increasing prevalence of kidney stone was observed with increased daily sitting time. However, the trend was not observed in individuals who participated in vigorous recreational activity, as they experienced a decreased risk of kidney stone despite having a daily sitting time of 6 to 8 hours (crude model OR=0.659, 95% CI: 0.457 to 0.950, P=0.028), indicating that vigorous recreational activity may partially attenuate the detrimental effect of prolonged sitting time. CONCLUSION: Our study revealed an increasing trend of prevalence of kidney stone with increased daily sitting time among the population not performing vigorous recreational activity despite the difference was nonsignificant. Vigorous recreational activity may modify the association between daily sitting time and kidney stone. More prospective cohort studies are warranted to further examine this association.

Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations.

BACKGROUND: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations. METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable. RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events. CONCLUSION: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.

BACKGROUND: The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes interact with immunocytes by secreting growth factors, cytokines, and chemokines, leading to wound healing, fibrosis, and escape of cancer immune surveillance. However, the specific mechanisms involved in the fibroblast-immunocyte interaction network have not yet been fully elucidated. MAIN BODY AND CONCLUSION: Therefore, we systematically reviewed the molecular mechanisms of fibroblast-immunocyte interactions in fibrosis, from the history of cellular evolution and cell subtype divisions to the regulatory networks between fibroblasts and immunocytes. We also discuss how these communications function in different tissue and organ statuses, as well as potential therapies targeting the reciprocal fibroblast-immunocyte interplay in fibrosis. A comprehensive understanding of these functional cells under pathophysiological conditions and the mechanisms by which they communicate may lead to the development of effective and specific therapies targeting fibrosis.

Accessing gold p-acid reactivity under electrochemical anode oxidation (EAO) through oxidation relay.

The gold π-acid activation under electrochemical conditions is achieved. While EAO allows easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far are limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications.

Sn and dual-oxygen-vacancy in the Z-scheme Bi2Sn2O7/Sn/NiAl-layered double hydroxide heterojunction synergistically enhanced photocatalytic activity toward carbon dioxide reduction.

Photocatalytic conversion of carbon dioxide (CO2) into high value-added chemicals is an attractive yet challenging process, primarily due to the readily recombination of hole-electron pairs in photocatalysts. Herein, dual-oxygen-vacancy mediated Z-scheme Bi2Sn2O7/Sn/NiAl-layered double hydroxide (VO,O-20BSL) heterojunctions were hydrothermally synthesized and subsequently modified with Sn monomers to enhance photocatalytic activity toward CO2 reduction. The abundance of oxygen vacancies endowed the VO,O-20BSL with extended optical adsorption, enhanced charges separation, and superior CO2 adsorption and activation. The interfacial charges transfer of the VO,O-20BSL was demonstrated to follow a Z-scheme mechanism via photochemical deposition of metal/metal oxide. Under visible light irradiation, the VO,O-20BSL exhibited the highest yields of carbon monoxide (CO) and methane (CH4), with values of 72.03 and 0.85 umol·g-1·h-1, respectively, which were 2.66 and 1.57 times higher than that of the VO-NiAl-layered double hydroxide (VO-1LDH). In situ diffuse reflectance infrared fourier transform spectroscopy (DRIFTS) revealed that carboxylic acid groups (COOH*) and aldehyde groups (CHO*) were the predominant intermediates during CO2 reduction, and accordingly, possible CO2 reduction pathways and mechanism were proposed. This study presents a feasible approach to incorporate dual vacancies into Z-scheme heterojunctions for CO2 reduction.

Effect of baseline cancer pain on the efficacy of immunotherapy in lung cancer patients.

Background: Cancer pain is a common symptom in cancer patients. However, few reports have evaluated the effect of baseline cancer pain on the efficacy of immunotherapy in lung cancer patients. The aim of this retrospective study is to reveal the effect of baseline cancer pain on the prognosis of lung cancer patients receiving immunotherapy. Methods: We retrospectively reviewed the medical records of lung cancer patients who received immunotherapy at Zhejiang Cancer Hospital and were included 280 patients with or without baseline cancer pain. Propensity score matching (PSM) was used to minimize potential selection bias. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier estimation and log-rank tests. Cox proportional hazard regression analysis was performed to identify factors associated with survival independence. Results: The median PFS and OS of the patients with baseline cancer pain were significantly shorter than that of patients without baseline cancer pain (PFS: 3.1 vs. 6.5 months, P=0.001; OS: 16.5 vs. 31.2 months, P<0.001). PSM also included 27 patients with or without breakthrough pain. Patients with breakthrough pain had significantly shorter median PFS and OS than those without breakthrough pain (PFS: 1.9 vs. 4.2 months, P=0.001; OS: 9.9 vs. 18.7 months, P=0.012). Cox analysis results implicated breakthrough pain as an independent prognostic factor for immunotherapy. Conclusions: Baseline cancer pain is a negative prognostic factor for lung cancer patients receiving immunotherapy. Patients with baseline cancer pain may have a worse survival prognosis if they develop breakthrough pain.

Efficacy and safety of immune checkpoint inhibitors in lung large-cell neuroendocrine carcinoma.

Background: Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare and highly aggressive neuroendocrine tumor. There is currently no standard therapeutic regimen, and systemic chemotherapy results in poor prognosis. Due to the rarity of L-LCNEC, the efficacy and safety of immune checkpoint inhibitors (ICIs) remain unclear. Methods: This study included 34 L-LCNEC patients administered ICIs at Zhejiang Cancer Hospital, from February 6, 2018 to February 6, 2023. The treatment responses were evaluated. Fisher's exact test was used to compare categorical variables, and the Kaplan-Meier method was used for survival analyses. Cox regression was used for multivariate analysis. Results: The objective response rate (ORR) of 34 patients was 29.4%, the disease control rate (DCR) was 82.4%, the median progression-free survival (PFS) was 6.30 months, and the median overall survival (OS) was 14.77 months. The ORRs of combined LCNEC (n=7) and pure LCNEC (n=27) were 14.3% and 33.3%; the DCRs were 100% and 77.8%; the median PFSs were 12.48 and 5.6 months (P=0.032); and the median OSs were 21.27 and 14.73 months, respectively (P=0.233). The observed incidence of immune-related adverse events (irAEs) was 61.8%, primarily occurring in grades 1/2 (58.8%) and grade 3 (5.9%). Elevated aminotransferases (14.7%), pneumonia (8.8%), and fatigue (8.8%) were the most common irAEs. Conclusions: ICIs treatment showed efficacy and safety in advanced L-LCNEC, with the potential for greater benefits in the combined LCNEC subtype.

Effects of intrapericardial administration after catheter drainage on malignant pericardial effusion in non-small cell lung cancer: A real-world study.

BACKGROUND: Malignant pericardial effusion (MPE) is a serious complication of cancer that can be potentially deadly. It usually occurs in advanced or terminal stages of the disease, and as a result, patients with MPE often have a poor prognosis. There is a limited amount of research available that directly compares the effectiveness and safety of intrapericardial drug administration following pericardial drainage versus catheter drainage alone in non-small cell lung cancer (NSCLC) patients who have MPE. METHODS: We retrospectively included 86 patients with NSCLC with MPE at Zhejiang Cancer Hospital. Survival and recurrence estimates were determined with the Kaplan-Meier method. RESULTS: We divided the 86 patients with NSCLC into two groups: a pericardial drainage group (34 out of 86, 39.5%) and an intrapericardial administration group (52 out of 86, 60.5%). The response rates were 70.6% and 76.9% (p = 0.510), respectively. The median OS was 132.0 and 234.0 days (p = 0.579), respectively. The median time to recurrent drainage was 43.0 and 104.0 days (p = 0.170), respectively. The incidence of adverse events (AEs) was 44.1% and 61.5% (p = 0.113), respectively. The most frequent AEs were pain (27.9%) and fever (24.4%). Additionally, two patients in the intrapericardial administration group died of cardiac arrest. CONCLUSIONS: Compared with catheter drainage alone, intrapericardial medication infusion during catheter drainage did not have significantly different effects. AEs require close monitoring and management.

The application of metagenomic next-generation sequencing in pathogen diagnosis: a bibliometric analysis based on Web of Science.

Background: Infectious disease is a large burden on public health globally. Metagenomic next-generation sequencing (mNGS) has become popular as a new tool for pathogen diagnosis with numerous advantages compared to conventional methods. Recently, research on mNGS increases yearly. However, no bibliometric analysis has systematically presented the full spectrum of this research field. Therefore, we reviewed all the publications associated with this topic and performed this study to analyze the comprehensive status and future hotspots of mNGS for infectious disease diagnosis. Methods: The literature was searched in the Web of Science Core Collection and screened without year or language restrictions, and the characteristics of the studies were also identified. The outcomes included publication years, study types, journals, countries, authorship, institutions, frontiers, and hotspots with trends. Statistical analysis and visualization were conducted using VOSviewer (version 1.6.16) and CiteSpace (version 6.1. R3). Results: In total, 325 studies were included in the analysis after screening. Studies were published between 2009 and 2022 with a significantly increasing number from 1 to 118. Most of the studies were original articles and case reports. Frontiers in Cellular and Infection Microbiology and Clinical Infectious Disease were the most commonly cited and co-cited journals. Institutions and researchers from China contributed the most to this field, followed by those from the USA. The hotspots and frontiers of these studies are pneumonia, tuberculosis, and central nervous system infections. Conclusion: This study determined that mNGS is a hot topic in the diagnosis of infectious diseases with development trends and provides insights into researchers, institutions, hotspots and frontiers in mNGS, which can offer references to related researchers and future research.

Efficacy of Tyrosine Kinase Inhibitors in Primary Driver-Gene-Positive Combined Small-Cell Lung Cancer: A Retrospective Study.

BACKGROUND: Combined small-cell lung cancer (c-SCLC) with gene mutations is a rare subtype often found alongside adenocarcinoma. Targeted therapy may be effective because of the presence of specific molecular targets. However, due to its rarity and unconventional genetic testing, the efficacy remains uncertain. METHODS: A total of 31 c-SCLC patients with gene mutations were retrospectively included and grouped according to their treatment regimens. Treatment outcomes were evaluated. Kaplan-Meier method was used for survival analysis, with Log Rank test applied for comparison between groups. RESULTS: We divided the 31 patients into 3 groups according to first-line treatment: group A (chemotherapy, n = 16), group B (targeted monotherapy, n = 7), and group C (targeted combination therapy, n = 8). The overall response rates (ORR) were 43.8%, 42.9%, and 62.5%. The disease control rates (DCR) were 87.5%, 85.7%, and 100%. The median progression-free survival (PFS) was 4.0, 5.0, and 7.93 months (P = .024), with a significant difference between group A and C (P = .010). The median overall survival (OS) was 14.10, 17.43, and 12.93 months (P = .313). Seven patients in group A received targeted therapy in later-line. Of the total 22 patients received targeted monotherapy or combination therapy, the ORR and DCR were 54.5% and 90.9%. The median PFS and OS were 5.87 and 17.30 months. Additionally, adverse events (AEs) occurred in 53.8% and 88.9% of monotherapy and combination therapy. The most common AEs in monotherapy were elevated transaminases (23.1%) and in combination anemia (66.7%). CONCLUSIONS: TKIs showed encouraging efficacy in driver-gene-positive c-SCLC. While monotherapy may be a supplementary option, combination with chemotherapy appears to be preferable and superior.

Accessing Gold π-Acid Reactivity under Electrochemical Anode Oxidation (EAO) through Oxidation Relay.

The gold π-acid activation under electrochemical condition is achieved for the first time. While EAO allowing easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications to come.

Sequential therapy with crizotinib and a second-generation ALK inhibitor versus direct therapy of a second-generation ALK inhibitor in ALK-positive advanced lung cancer: a real-world study.

Background: There are few real-world studies in which the efficacy of sequential crizotinib and second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are compared with direct therapy of second-generation ALK TKI in ALK-positive advanced lung cancer. Methods: Between May 2014 and October 2022, 211 patients from the Zhejiang Cancer Hospital who harbored ALK rearrangement were analyzed. Of these patients, 115 received crizotinib with sequential second-generation ALK TKIs, and 96 patients received a second-generation ALK TKI directly. The survival analysis of median progression-free survival (PFS), overall survival (OS), and central nervous system time to progression (CNS TTP) in the various groups were calculated using the Kaplan-Meier method and compared by the log-rank test. Results: Of the 211 lung cancer patients with ALK rearrangement, there were no statistical differences in PFS (25.27 vs. 20.47 months, P=0.644) and OS (70.27 months vs. not reached, P=0.991) between the 115 patients in the sequential therapy group and the 96 patients in the direct second-generation group. In the patients with baseline brain metastases at study entry (n=54), the sequential therapy group had a significantly shorter median CNS TTP than the direct second-generation group (10.40 vs. 22.40 months, P=0.040). Multivariate analyses revealed that the prognostic factors for PFS included performance status (PS, P=0.047) and brain metastases (P=0.010). For OS, the prognostic factors included PS (P=0.047) and liver metastases (P=0.021). Conclusions: There was no statistical difference in efficacy between first-generation sequential second-generation ALK TKIs and direct therapy of second-generation ALK TKI regimens. The CNS efficacy of the direct second-generation group was better than that of the sequential therapy group. The prognostic factors for PFS included PS and brain metastases, while the prognostic factors for OS, PS and liver metastases were included.

Gold-Catalyzed Amine Cascade Addition to Diyne-Ene: Enantioselective Synthesis of 1,2-Dihydropyridines.

With the well-documented chemical and biological applications, piperidine and pyridine are among the most important N-heterocycles, and a new synthetic strategy, especially one with an alternative bond-forming design, is of general interest. Using the gold-catalyzed intermolecular condensation of amine and diyne-ene, we report herein the first example of enantioselective 1,2-dihydropyridine synthesis through a formal [3+2+1] fashion (up to 95 % yield, up to 99 % e.e.).

Clinical outcomes of immune checkpoint inhibitors to treat non-small cell lung cancer patients harboring epidermal growth factor receptor mutations.

BACKGROUND: We aimed to determine the clinical. outcomes of various immune checkpoint inhibitor (ICI) combinations for the treatment of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. The results predicted the treatment efficacy of these combinations. METHODS: From July 15, 2016 to March 22, 2022, 85 NSCLC patients with EGFR mutations, enrolled at the Zhejiang Cancer Hospital, received ICI combinations after resistance to prior EGFR-tyrosine kinase inhibitors (EGFR-TKIs). These patients were diagnosed with EGFR mutations using an amplification refractory mutation system PCR (ARMS-PCR) and next-generation sequencing (NGS). Survival times were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: Patients who received ICIs combined with anti-angiogenic therapy had longer progression-free survival (PFS) and overall survival (OS) than patients who received ICIs combined with chemotherapy. There was no significant difference in survival time between patients who received ICIs combined with chemotherapy and anti-angiogenic therapy and patients who received ICIs combined with anti-angiogenic therapy or ICIs combined with chemotherapy, which was due to the limitation sample size of patients who received ICIs combined with chemotherapy and anti-angiogenic therapy. Patients with L858R mutations had a longer PFS and OS than patients with exon 19 deletions. T790M negative patients benefited more from ICI combinations, compared with T790M positive patients. In addition, there was no significant difference in PFS and OS between patients with TP53 co-mutations and patients without a TP53 co-mutation. We also found that patients with prior first-generation EGFR-TKI resistance had longer PFS and OS than prior third-generation EGFR-TKI resistance patients. There was no new adverse event in this study. CONCLUSIONS: EGFR-mutated patients who received ICIs combined with anti-angiogenic therapy had longer PFS and OS than patients with ICIs combined with chemotherapy. Patients with L858R or without T790M mutation benefited more from ICI combinations. Besides, patients with prior first-generation EGFR-TKI resistance could benefit more from ICIs combinations than prior third-generation EGFR-TKI resistance patients.

Efficacy and safety of immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy for thymic epithelial tumors (TETs): a retrospective study.

Background: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown promising antitumor activity against a range of advanced cancers. However, evidence is lacking as to whether this combination therapy could benefit thymic epithelial tumors (TETs). We aimed to explore the efficacy and safety of this combination therapy in advanced TETs. Methods: Ten patients with pathologically proven advanced TETs who received ICIs combined with an antiangiogenic agent from 2020 to 2022 at Zhejiang Cancer Hospital were included in the study. The Kaplan-Meier method was used to compare the treatment efficacy and survival outcomes. Results: Of the cohort of ten patients who received immunotherapy combined with antiangiogenic targeting drugs, two patients achieved a partial response (PR) with an objective response rate of 20% and seven patients achieved stable disease (SD) with a disease control rate (DCR) of 90%. The median progression-free survival (PFS) was 6.7 months [95% confidence interval (CI): 3.35-8.515] and the median overall survival (OS) was 45.6 months (95% CI: 3.265-88.001). Grade 3 treatment-related adverse events (TRAEs) were only detected in one patient. No grade 4 or above TRAEs were observed. Conclusions: ICIs in combination with antiangiogenic targeted drugs may be a promising treatment for advanced TETs.

Clinical outcomes of immune checkpoint inhibitor therapy for advanced lung adenosquamous carcinoma.

Background: Primary adenosquamous carcinoma (ASC) of the lung is a rare and aggressive disease and limited information is available on the efficacy of immune checkpoint inhibitors (ICIs) for this disease. Here, we evaluated the expression status of programmed death-1 ligand 1 (PD-L1) and efficacy of ICIs in patients with pulmonary ASC. Methods: The efficacy and toxicity of ICIs were examined in 38 patients with previously treated lung ASC from November 2017 to October 2021 in Zhejiang Cancer Hospital (Hangzhou, China). Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. Results: A total of 38 patients with ASC were included in this retrospective study. ICI treatment induced an objective response rate (ORR) of 23.7% and a disease control rate (DCR) of 86.8%. The median progression-free survival (PFS) and median overall survival (OS) were 5.47 and 24.10 months, respectively. Seventeen patients were successfully evaluated for PD-L1 expression status, with 11 (64.7%) identified as PD-L1-positive. ORR and DCR for PD-L1-positive patients were 36.4% (4/11) and 100% (11/11) and the corresponding values for PD-L1-negative patients were 0 (0/6) and 50% (3/6), respectively. The median PFS of PD-L1-positive and PD-L1-negative patient groups was 5.00 and 1.90 months (P=0.166) while the median OS was 11.30 months and not reached, respectively (P=0.966). The incidence rate of immune-related adverse events (irAEs) was 52.6%, with 13.2% grade 3-4 irAEs. The most common irAEs were malaise and pneumonitis. One patient died of pneumonitis during the study. Conclusions: ICIs show considerable potential as a treatment option for lung ASC. PFS and OS rates are similar for PD-L1-positive and PD-L1-negative patients. Further large-scale studies are required to establish the relationship between PD-L1 expression and response to ICIs in ASC.