Design of Thermally Activated Delayed Fluorescence Materials: Transition from Carbonyl to Amide-Based Acceptors.

Benzophenone skeletons containing a carbonyl unit (O=C) have been widely used as electron acceptors in the thermally activated delayed fluorescence (TADF) materials. Herein, we present a novel molecular design concept for TADF materials by transitioning from a carbonyl to an amide (O=C-N) skeleton as the acceptor. The amide unit, compared to its carbonyl counterpart, offers a more stable electronic configuration. Leveraging this insight, we have developed a series of high-performance TADF molecules based on benzoyl carbazole and carbazoline acceptors. These molecules exhibit exceptionally small singlet-triplet energy gaps and pronounced aggregation-enhanced emission properties, achieving photoluminescence quantum yields in neat films as high as 99%. Consequently, these materials serve as efficient emitters in non-doped organic light-eimtting diodes (OLEDs), reaching a maximum quantum efficiency (EQEmax) of up to 26.0%, significantly higher than the 17.0% obtained with benzophenone acceptor-based TADF molecules. Additionally, they have been used as TADF hosts in narrowband red fluorescent OLEDs, setting a record-high EQEmax of 22.4%.

Construction of a ferroptosis and hypoxia-related gene signature in cervical cancer to assess tumour immune microenvironment and predict prognosis.

BACKGROUND: This study aimed to investigate the potential role of ferroptosis/hypoxia-related genes in cervical cancer to improve early management and treatment of cervical cancer. METHODS: All data were downloaded from public databases. Ferroptosis/hypoxia-related genes associated with cervical cancer prognosis were selected to construct a risk score model. The relationship between risk score and clinical features, immune microenvironment and prognosis were analysed. RESULTS: Risk score model was constructed based on eight signature genes. Drug prediction analysis showed that bevacizumab and cisplatin were related to vascular endothelial growth factor A. Risk score, as an independent prognostic factor of cervical cancer, had a good survival prediction effect. The two groups differed significantly in degree of immune cell infiltration, gene expression, tumour mutation burden and somatic variation. CONCLUSIONS: We developed a novel prognostic gene signature combining ferroptosis/hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer.

Ferroptosis, hypoxia and immune regulation play important roles in cervical cancer progression. In this study, we developed a novel prognostic signature combining ferroptosis and hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer patients. The risk score established by ferroptosis and hypoxia-related gene as an independent prognostic factor of cervical cancer has a good survival prediction effect. High and low risk groups showed significant differences in TIME, prognosis, biological metabolic pathway and tumour mutation burden. In addition, we found drugs associated with signature genes. In short, this study has laid a theoretical foundation for exploring the related molecular mechanisms and prognosis of cervical cancer. It also contributes to the exploration of clinical management and treatment.

Validity of the modified versions of SARC-F+EBM for sarcopenia screening and diagnosis in China: the PPLSS study.

BACKGROUND AND OBJECTIVES: It is recommended by Asian Working Group for Sarcopenia to early identify people at risk for sarcopenia using simple screening tools like SARC-F. The modified version SARC-F+EBM showed higher diagnostic performance. However, this cut-off value of body mass index (BMI) remained uncertain to be used in Chinese population. In this study, we used appropriate BMI recommended for Chinese older population and further modified SARC-F+EBM by combining calf circumference. METHODS AND STUDY DESIGN: Diagnostic tests were performed and the receiver operating characteristics analyses were conducted between the SARC-F, SARC-F+EBM (cut-off of BMI: ≤ 21 kg/m2), SARC-F+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2), SARC-CalF and SARC-CalF+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2) in 1660 community-dwelling participants aged ≥ 65 years from China. RESULTS: The participants had an average age of 71.7±5.1 years, of which 56.8% were women. All the modified models could enhance the areas under the receiver operating characteristic curve (AUC) of original SARC-F (all p<0.001). The SARC-F+EBM (CN) also showed a significantly higher sensitivity of 47.4% (p<0.001) and an AUC of 0.809 (p=0.005) than SARC-F+EBM. SARC-CalF+EBM (CN) was validated to be of great diagnostic value of the highest AUC of 0.88 among these sarcopenia screening tools, including SARC-F, SARC-CalF and SARC-F+EBM (CN) (all p<0.001). Using this study population as a reference, the optimal cut-off value of SARC-CalF+EBM (CN) is ≥12 points, with a sensitivity of 79.3% and a specificity of 80.7%. CONCLUSIONS: The SARC-F+EBM (CN) and SARC-CalF+EBM (CN) could enhance the diagnostic performance of SARC-F and SARC-F+EBM and are suitable sarcopenia screening tools for Chinese population.

Unlocking Structurally Nontraditional Naphthyridine-Based Electron-Transporting Materials with C-H Activation-Annulation.

The inherent benefits of C-H activation have given rise to innovative approaches in designing organic optoelectronic molecules that depart from conventional methods. While theoretical calculations have suggested the suitability of the 2,6-naphthyridine scaffold for electron transport materials (ETMs) in organic light-emitting diodes (OLEDs), the existing synthetic methodologies have proven to be insufficient for the construction of multiple arylated and fully aryl-substituted molecules. Herein, we present a solution for the synthesis of 2,6-naphthyridine derivatives, with the rhodium-catalyzed consecutive C-H activation-annulation process of fumaric acid with alkynes standing as the pivotal step within this strategy. The ETMs, purposefully designed and synthesized based on the 2,6-naphthyridine framework, exhibit an impressively high glass-transition temperature (Tg) of 282 °C and high electron mobility (µe), setting a new benchmark for ETMs in OLEDs with a µe exceeding 10-2 cm2 V-1 s-1. These materials prove to be versatile ETM candidates suitable for red, green, and blue phosphorescent OLED devices.

Application of 3.0 T multimodal MRI in FIGO staging of cervical cancer.

BACKGROUND: In malignant tumours of the female reproductive system, cervical cancer is second only to breast cancer, seriously threatening the health and safety of most women. OBJECTIVE: To evaluate the clinical value of 3.0 T multimodal nuclear magnetic resonance imaging (MRI) in the International Federation of Gynecology and Obstetrics' (FIGO) staging of cervical cancer. METHODS: The clinical data of 30 patients with pathologically diagnosed cervical cancer admitted to our hospital from January 2018 to August 2022 were analysed retrospectively. Before treatment, all patients were examined with conventional MRI, diffusion-weighted imaging and multi-directional contrast-enhanced imaging. RESULTS: The accuracy of multimodal MRI in the FIGO staging of cervical cancer (29/30, 96.7%) was significantly higher than the accuracy obtained in a control group (21/30, 70.0%), with a statistically significant difference (p= 0.013). In addition, there was good agreement between two observers applying multimodal imaging (kappa= 0.881) and moderate agreement between two observers in the control group (kappa= 0.538). CONCLUSION: Multimodal MRI can evaluate cervical cancer comprehensively and accurately to enable accurate FIGO staging, providing significant evidence for clinical operation planning and subsequent combined therapy.

Application of Magnetic Resonance Diffusion Tensor Imaging in Diagnosis of Lumbosacral Nerve Root Compression

OBJECTIVE: The aim of this study was to assess the value of 3.0T magnetic resonance (MR) Diffusion tensor imaging (DTI) in the diagnosis of lumbosacral nerve root compression. METHODS: The radiology reports, and clinical records of 34 patients with nerve root compression caused by lumbar disc herniation or bulging and 21 healthy volunteers who had undergone magnetic resonance imaging (MRI) and DTI scan were retrospectively reviewed. The differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between compressed and non-compressed nerve roots from patients and the normal nerve roots from healthy volunteers were compared. Meanwhile, the nerve root fiber bundles were observed and analyzed. RESULTS: The average FA and ADC values of the compressed nerve roots were 0.254 ± 0.307 and 1.892 ± 0.346 10^-3mm2/s, respectively. The average FA and ADC values of the non-compressed nerve roots were 0.377 ± 0.659 and 1.353 ± 0.344 10^-3mm2/s, respectively. The FA value of compressed nerve roots was significantly lower than that of non-compressed nerve roots (P < 0.01). The ADC value of compressed nerve roots was significantly higher than that of non-compressed nerve roots. There were no significant differences between the left and right nerve roots of normal volunteers in FA and ADC values (P > 0.05). The nerve roots at different levels of L3-S1 had significantly different FA and ADC values (P < 0.01). Incomplete fiber bundles with extrusion deformation, displacement or partial defect were observed in the compressed nerve root fiber bundles. The real diagnosis of the clinical situation of the nerve can provide neuroscientists with an important computer tool to help them infer and understand the possible working mechanism from the experimental data of behavior and electrophysiology. CONCLUSION: The compressed lumbosacral nerve roots can be accurately localized through 3.0T magnetic resonance DTI, which is instructive for accurate clinical diagnosis and preoperative localization.

The Association of the Triglyceride and Muscle to Fat Ratio During Early Pregnancy with the Development of Gestational Diabetes Mellitus.

Objective: This study explored the association between metabolic factors and body composition during the first trimester of gestational diabetes mellitus (GDM). Methods: This prospective study recruited pregnant women in their first trimester. Clinical information and glucose and lipid measurements were collected, and body composition was assessed using multifrequency bioelectrical impedance analysis. GDM was diagnosed on the basis of an oral glucose tolerance test at 24-28 gestational week. Factors related to GDM were investigated using correlation, and risk ratios (RRs) and 95% CIs of potential risk factors with GDM were estimated using Poisson regression. The area under the receiver operating characteristic (ROC) curve was used to determine predictive effects. Results: 59/302 women (19.5%) developed GDM. Older (RR 1.076, 95% CI 1.005-1.152), higher body mass index (BMI) before pregnancy (pre-BMI) (RR 1.012, 95% CI 1.005-1.063), triglycerides (RR 4.052, 95% CI 1.641-6.741), and lower skeletal muscle mass (SMM) to fat mass (FM) ratio (SMM/FM) (RR 0.213, 95% CI 0.051-0890) in the first trimester, and family history of type 2 diabetes (RR 1.496, 95% CI 1.014-2.667) significantly associated with the risk of GDM, but neither fasting plasma glucose nor glycated albumin was associated with GDM. The combined multivariate prediction model achieved good discrimination with an AUC of 0.806 (95% CI 0.737-0.895, P<0.001). According to ROC curve, the cut-off values of TG and SMM/FM were 0.925 mmol/L and 1.305. Conclusion: Reduced SMM/FM and elevated triglyceride (TG) levels in the first trimester are associated with GDM development, and should be screened in early pregnancy to identify high-risk subjects for GDM.

Innovative strategy for the conservation of a millennial mausoleum from biodeterioration through artificial light management.

Artificial lights can cause critical microbial biodeterioration of heritage monuments by promoting the outbreak of phototrophic microbiomes when they are used for touristic viewing. Here, with the ultimate aim of providing innovative solutions for the conservation and visiting of such monuments, we conducted a pioneering two-year in situ manipulative experiment to evaluate the impacts of different artificial light wavelengths (i.e., blue, green and red lights compared to white light) on the phototrophic microbiome of a millennial Chinese imperial mausoleum. Our results show that artificial light can shape the ecophysiological features of the phototrophic bacteriome in this monument and reduce its potential for further biodeterioration. In general, Cyanobacteria dominated (42.0% of the total relative abundance) the phototrophic bacteriome of this cultural relic; however, they were also very sensitive to the choice of artificial light. Compared to white light, monochromatic light, especially green light, reduced Cyanobacteria abundances (18.6%) by decreasing photosynthetic pigment abundances (42.9%); decreased the abundances of heterotrophic species belonging to Proteobacteria (4.5%) and the proportion of genes (6.1%) associated with carbon (i.e., carbon fixation), nitrogen (i.e., denitrification), and sulfur (i.e., dissimilatory sulfate reduction) cycling; and further decreased organic acid (10.1-14.1%) production of the phototrophic bacteriome, which is known to be involved in biodeterioration. Taken together, our findings constitute a major advancement in understanding how light wavelengths influence the phototrophic microbiome in cultural relics, and we found that artificial lights with certain wavelengths (e.g., green light) can help long-term conservation while allowing tourism activities.

Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study.

BACKGROUND: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer. METHODS: HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe. Eligible patients were aged 18 years or older with HER2-amplified biliary tract cancer confirmed by in-situ hybridisation per central testing, at least one measurable target lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were assigned into cohorts based on HER2 immunohistochemistry (IHC) score: cohort 1 (IHC 2+ or 3+; HER2-positive) and cohort 2 (IHC 0 or 1+). Patients received zanidatamab 20 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate in cohort 1 as assessed by independent central review. Anti-tumour activity and safety were assessed in all participants who received any dose of zanidatamab. This trial is registered with ClinicalTrials.gov, NCT04466891, is ongoing, and is closed to recruitment. FINDINGS: Between Sept 15, 2020, and March 16, 2022, 87 patients were enrolled in HERIZON-BTC-01: 80 in cohort 1 (45 [56%] were female and 35 [44%] were male; 52 [65%] were Asian; median age was 64 years [IQR 58-70]) and seven in cohort 2 (five [71%] were male and two [29%] were female; five [71%] were Asian; median age was 62 years [IQR 58-77]). At the time of the data cutoff (Oct 10, 2022), 18 (21%) patients (17 in cohort 1 and one in cohort 2) were continuing to receive zanidatamab; 69 (79%) discontinued treatment (radiographic progression in 64 [74%] patients). The median duration of follow-up was 12·4 months (IQR 9·4-17·2). Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41·3% [95% CI 30·4-52·8]). 16 (18%) patients had grade 3 treatment-related adverse events; the most common were diarrhoea (four [5%] patients) and decreased ejection fraction (three [3%] patients). There were no grade 4 treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive biliary tract cancer. These results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer. FUNDING: Zymeworks, Jazz, and BeiGene.

Chronic diflubenzuron exposure causes reproductive toxic effects in female marine medaka (Oryzias melastigma).

Diflubenzuron, an insecticide commonly used in marine fish farming, has been detected in various marine environments. However, its potential impact on marine fish remains largely unknown. This study investigated the reproductive toxicity of chronic diflubenzuron exposure in female marine medaka (Oryzias melastigma). Marine medaka were exposed continuously to environmentally relevant concentrations of diflubenzuron (0.1, 1, and 10 µg/L) or a solvent control from the fertilized egg to adulthood. In exposed female marine medaka, the gonadosomatic index (GSI) and the number of laid eggs were significantly reduced. Moreover, diflubenzuron-exposed female marine medaka showed altered ovarian histopathology, with an increased relative proportion of immature oocytes and atretic follicles and a decreased relative proportion of mature oocytes. Maternal exposure to diflubenzuron also inhibited the development of the F1 generation, significantly reducing the hatching rate of F1 embryos and significantly increasing the malformation rate of F1 larvae. Furthermore, changes in hormone levels and expression of genes along the hypothalamus-pituitary-gonad-liver (HPGL) axis were observed, which may be the fundamental reason for all the reproductive toxic effects mentioned above. These results provide new insights into the impact of diflubenzuron on the female marine medaka reproductive system and underscore the importance of investigating the potential environmental risks of diflubenzuron in the marine environment.

An integrative analysis of enhancer of yellow 2 homolog (ENY2) as a molecular biomarker in pan-cancer.

ENY2 (Enhancer of yellow 2 transcription factor) is a transcription nuclear protein and primarily participates in the course of mRNA export and histone deubiquitination to influence gene expression. Current studies have shown that the expression of ENY2 is significantly upregulated in multiple cancers. However, the exact association between ENY2 and pan-cancers has not been fully established. Here, we comprehensively analyzed ENY2 from the online public database and The Cancer Genome Atlas (TCGA) database, including gene expression level in pan-cancer, comparison of ENY2 expression in different molecular and immune subtypes of pan-cancer, targeted protein, biological functions, molecular signatures, diagnostic and prognostic value in pan-cancer. Moreover, we focused on head and neck squamous cell carcinoma (HNSC) and explored ENY2 from the perspective of the correlations with clinical characteristics, prognosis, co-expression genes, differentially expressed genes (DEGs) and immune Infiltration. Our findings showed that the expression of ENY2 differed enormously not only in most cancer types but also in different molecular and immune subtypes of cancers. High accuracy in predicting cancers and notable correlations with prognosis of certain cancers suggested that ENY2 might be a potential diagnostic and prognostic biomarker of cancers. In addition, ENY2 was identified to be significantly correlated with clinical stage, gender, histologic grade and lymphovascular invasion in HNSC. Overexpression of ENY2 could lead to a worse overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HNSC, especially in different clinical subgroups of HNSC. Taken together, ENY2 showed strong correlation with the diagnosis and prognosis of pan-cancer, and was an independent prognostic risk factor of HNSC, which may serve as a potential target for cancer management.

Association of dietary fat intake with skeletal muscle mass and muscle strength in adults aged 20-59: NHANES 2011-2014.

Background: Sarcopenia, a progressive loss of skeletal muscle mass and strength, needs to initially prevent in the twenties. Meanwhile, there is a lack of research on the effects of fat consumption on skeletal muscle mass and strength in adults aged 20-59. We aimed to assess associations between dietary fat intake and skeletal muscle mass, as measured by appendicular lean mass adjusted for body mass index (ALMBMI), and muscle strength, as represented by handgrip strength adjusted for body mass index (GSMAXBMI), among adults aged 20-59. Methods: Dietary fat intake per kilogram of actual body weight was assessed using two 24h recalls, while ALM and GSMAX were measured using DXA and a handgrip dynamometer, respectively. A weighted multiple linear regression model was employed to analyze the association between dietary fat intake and skeletal muscle mass, utilizing data from the National Health and Nutrition Examination Survey spanning from 2011 to 2014. To assess the non-linear relationship and saturation value between dietary fat intake and skeletal muscle mass, a smooth curve fitting approach and a saturation effect analysis model were utilized. Results: The study comprised a total of 5356 subjects. After adjusting for confounding factors, there was a positive association observed between dietary fat intake and ALMBMI as well as GSMAXBMI. The relationship between dietary fat intake and ALMBMI showed an inverted U-shaped curve, as did the association with GSMAXBMI. Turning points were observed at 1.88 g/kg/d for total fat intake and ALMBMI, as well as at 1.64 g/kg/d for total fat intake and GSMAXBMI. Furthermore, turning points were still evident when stratifying by gender, age, protein intake, and physical activity. The turning points were lower in individuals with low protein intake(<0.8 g/kg/d) and high levels of physical activity. Conclusion: The moderate dietary fat intake can be beneficial for muscle mass and strength in adults aged 20-59 under specific conditions. Special attention should be directed toward the consumption of fats in individuals with low protein intake and those engaged in high levels of physical activity.

Clinical Observations of Percutaneous Tibial Nerve Stimulation Combined with Sacral Nerve Root Magnetic Stimulation for the Treatment of Male Chronic Pelvic Pain and Chronic Prostatitis

Purpose: To investigate the clinical efficacy of percutaneous tibial nerve stimulation combines sacral nerve root magnetic stimulation in the treatment of chronic pelvic pain syndrome and chronic prostatitis. Methods: 60 male patients diagnosed with chronic pelvic pain syndrome or chronic prostatitis were analyzed in this study. Patients in the experimental group were treated with percutaneous tibial nerve stimulation (7 Hz) combined with sacral nerve root magnetic stimulation (5 Hz) whilst patients in the control group receiving treatment with only percutaneous tibial nerve stimulation. The National Institutes of Health-Chronic Prostatitis Symptom Index was used to evaluate prostatitis in the 2 groups before and at 4 weeks after treatment. Results: All patients showed improvements in scores before and after treatment in the two groups (p < 0.05). Further comparison between the two groups showed that patients in the experimental experienced more significant improvements in each of the indicators compare that to the control group patients (p < 0.05). Conclusions: Both percutaneous tibial nerve stimulation and percutaneous tibial nerve stimulation combined with magnetic stimulation of the sacral nerve roots have benefits for patients, but the benefits are more excellent when used together than when used alone. (AU)

Environmental Difference and Spatial Distance Affect the Fidelity of Variation Source of Microbial Community Structure in Air-Dried Soils.

Air-dried soil archives are important for microbial ecology research, although the process of air-drying preservation inevitably destroys the original microbial information in soils. Only upon fully understanding the limitations of air-dried soil can it play a greater role. The value of air-dried soil depends on the fidelity of microbial community structure information in the air-dried soil relative to that in fresh soil. To evaluate this, high-throughput sequencing was applied to investigate the microbial community of fresh soils and 227 days air-dried archives from typical farmland under a large spatial scale, and PERMANOVA was used to analyze the explanation proportion (EP) of the spatial factor on the microbial community structure in any paired-fresh or air-dried soils. The results show that for any paired soils, the value of EP ranged from 42.4% to 97.9% (p < 0.001). Importantly, taking fresh soil as a reference, the value of EP declined in air-dried soils (effect size r = 0.79, p < 0.001). Furthermore, the standardized difference in EP between fresh and air-dried soil (NDEP) was used to characterize the fidelity of variance source of microbial community structure in air-dried soils, and correlation tests showed that NDEP was negatively correlated with spatial distance (r = −0.21, p < 0.01) and with environmental difference (r = −0.37, p < 0.001). Further analyses show that larger NDEP was observed at a spatial distance <25 km or an environmental difference <0.58. Variance partitioning analysis showed that 28.0% of the variation in NDEP could be explained, with environmental difference constituting 14.0% and the interaction between the environmental difference and spatial distance constituting the remaining 14.0%. Soil texture was the most important factor for predicting NDEP, followed by soil pH and annual average temperature. This study not only emphasizes the possible decline in EP when using air-dried soils to reveal microbial community patterns, but also implies that air-dried soil is more suitable for addressing scientific questions under a large spatial scale or environmental differences.

Examining the Impact of Tislelizumab Added to Chemotherapy on Health-Related Quality-of-Life Outcomes in Previously Untreated Patients With Nonsquamous Non-Small Cell Lung Cancer.

PURPOSE: This study assessed the effects of tislelizumab, a programmed cell death protein 1 inhibitor, in combination with chemotherapy versus chemotherapy alone as first-line treatment on health-related quality of life (HRQoL) in patients with advanced nonsquamous non-small cell lung cancer (nSQ-NSCLC). METHODS: Patients in this randomized, open-label, multicenter phase III study RATIONALE 304 (NCT03663205) with histologically confirmed stage IIIB/IV nSQ-NSCLC were randomized 2:1 to tislelizumab plus platinum-pemetrexed (arm T + PP) or platinum-pemetrexed alone (arm PP). Health-related QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer. Key patient-reported outcome endpoints include mean score change from baseline at weeks 12 (during chemotherapy) and 18 (following chemotherapy) in the 30-item Quality of Life Questionnaire Core's global health status/quality of life (GHS/QoL) and time to deterioration in GHS/QoL. RESULTS: Three hundred thirty-two patients received at least 1 dose of study drug and completed at least 1 HRQoL assessment. Global health status/QoL score improved in arm T + PP at week 18 (between-group least square mean difference, 5.7; 95% confidence interval [CI], 1.0-10.5; P = 0.018). Patients in arm T + PP experienced greater reduction in coughing (-5.9; 95% CI, -11.6 to -0.1; P = 0.044), dyspnea (-3.8; 95% CI, -7.8 to 0.1; P = 0.059), chest pain (-6.2; 95% CI, -10.8 to -1.6; P = 0.008), and peripheral neuropathy (-2.6; 95% CI, -5.5 to 0.2; P = 0.066). Median time to deterioration in GHS/QoL was not achieved for either arm. DISCUSSION: The addition of tislelizumab to platinum-based chemotherapy was associated with improvements in nSQ-NSCLC patients' HRQoL as well as the important disease-specific symptoms of coughing, chest pain, and dyspnea.ClinicalTrials.gov Identifier: NCT03663205.

Organic and Inorganic Amendments Shape Bacterial Indicator Communities That Can, In Turn, Promote Rice Yield.

The dynamic patterns of the belowground microbial communities and their corresponding metabolic functions, when exposed to various environmental disturbances, are important for the understanding and development of sustainable agricultural systems. In this study, a two-year field experiment with soils subjected to: chemical fertilization (F), mushroom residues (MR), combined application of chemical fertilizers and mushroom residues (MRF), and no-fertilization (CK) was conducted to evaluate the effect of fertilization on the soil bacterial taxonomic and functional compositions as well as on the rice yield. The highest rice yield was obtained under MRF. Soil microbial properties (microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), urease, invertase, acid phosphatase, and soil dehydrogenase activities) reflected the rice yield better than soil chemical characteristics (soil organic matter (SOM), total N (TN), total K (TK), available P (AP), available K (AK), and pH). Although the dominant bacterial phyla were not significantly different among fertilizations, 10 bacterial indicator taxa that mainly belonged to Actinobacteria (Nocardioides, Marmoricola, Tetrasphaera, and unclassified Intrasporangiaceae) with functions of xenobiotic biodegradation and metabolism and amino acid and nucleotide metabolism were found to strongly respond to MRF. Random Forest (RF) modeling further revealed that these 10 bacterial indicator taxa act as drivers for soil dehydrogenase, acid phosphatase, pH, TK, and C/N cycling, which directly and/or indirectly determine the rice yield. Our study demonstrated the explicit links between bacterial indicator communities, community function, soil nutrient cycling, and crop yield under organic and inorganic amendments, and highlighted the advantages of the combined chemical and organic fertilization in agroecosystems.