The association between gray matter volume in the hippocampal subfield and antidepressant efficacy mediated by abnormal dynamic functional connectivity.

An abnormality of structures and functions in the hippocampus may have a key role in the pathophysiology of major depressive disorder (MDD). However, it is unclear whether structure factors of the hippocampus effectively impact antidepressant responses by hippocampal functional activity in MDD patients. We collected longitudinal data from 36 MDD patients before and after a 3-month course of antidepressant pharmacotherapy. Additionally, we obtained baseline data from 43 healthy controls matched for sex and age. Using resting-state functional magnetic resonance imaging (rs-fMRI), we estimated the dynamic functional connectivity (dFC) of the hippocampal subregions using a sliding-window method. The gray matter volume was calculated using voxel-based morphometry (VBM). The results indicated that patients with MDD exhibited significantly lower dFC of the left rostral hippocampus (rHipp.L) with the right precentral gyrus, left superior temporal gyrus and left postcentral gyrus compared to healthy controls at baseline. In MDD patients, the dFC of the rHipp.L with right precentral gyrus at baseline was correlated with both the rHipp.L volume and HAMD remission rate, and also mediated the effects of the rHipp.L volume on antidepressant performance. Our findings suggested that the interaction between hippocampal structure and functional activity might affect antidepressant performance, which provided a novel insight into the hippocampus-related neurobiological mechanism of MDD.

Analysis of the Spatial-Temporal Distribution Characteristics of Climate and Its Impact on Winter Wheat Production in Shanxi Province, China, 1964-2018.

The possible influence of global climate changes on agricultural production is becoming increasingly significant, necessitating greater attention to improving agricultural production in response to temperature rises and precipitation variability. As one of the main winter wheat-producing areas in China, the temporal and spatial distribution characteristics of precipitation, accumulated temperature, and actual yield and climatic yield of winter wheat during the growing period in Shanxi Province were analysed in detail. With the utilisation of daily meteorological data collected from 12 meteorological stations in Shanxi Province in 1964-2018, our study analysed the change in winter wheat yield with climate change using GIS combined with wavelet analysis. The results show the following: (1) Accumulated temperature and precipitation are the two most important limiting factors among the main physical factors that impact yield. Based on the analysis of the ArcGIS geographical detector, the correlation between the actual yield of winter wheat and the precipitation during the growth period was the highest, reaching 0.469, and the meteorological yield and accumulated temperature during this period also reached its peak value of 0.376. (2) The regions with more suitable precipitation and accumulated temperature during the growth period of winter wheat in the study area had relatively high actual winter wheat yields. Overall, the average actual yield of the entire region showed a significant increasing trend over time, with an upward trend of 47.827 kg ha-1 yr-1. (3) The variation coefficient of winter wheat climatic yield was relatively stable in 2008-2018. In particular, there were many years of continuous reduction in winter wheat yields prior to 2006. Thereafter, the impact of climate change on winter wheat yields became smaller. This study expands our understanding of the complex interactions between climate variables and crop yield but also provides practical recommendations for enhancing agricultural practices in this region.

Interspecific competition prevents the proliferation of social cheaters in an unstructured environment.

Bacterial communities are intricate ecosystems in which various members interact, compete for resources, and influence each other's growth. Antibiotics intensify this complexity, posing challenges in maintaining biodiversity. In this study, we delved into the behavior of kin bacterial communities when subjected to antibiotic perturbations, with a particular focus on how interspecific interactions shape these responses. We hypothesized that social cheating-where resistant strains shield both themselves and neighboring cheaters-obstructed coexistence, especially when kin bacteria exhibited varied growth rates and antibiotic sensitivities. To explore potential pathways to coexistence, we incorporated a third bacterial member, anticipating a shift in the dynamics of community coexistence. Simulations and experimental bacterial communities confirmed our predictions, emphasizing the pivotal role of interspecific competition in promoting coexistence under antibiotic interference. These insights are crucial for understanding bacterial ecosystem stability, interpreting drug-microbiome interactions, and predicting bacterial community adaptations to environmental changes.

Gut Distribution, Impact Factor, and Action Mechanism of Bacteriocin-Producing Beneficial Microbes as Promising Antimicrobial Agents in Gastrointestinal Infection.

Gastrointestinal (GI) infection by intestinal pathogens poses great threats to human health, and the therapeutic use of antibiotics has reached a bottleneck due to drug resistance. The developments of antimicrobial peptides produced by beneficial bacteria have drawn attention by virtue of effective, safe, and not prone to developing resistance. Though bacteriocin as antimicrobial agent in gut infection has been intensively investigated and reviewed, reviews on that of bacteriocin-producing beneficial microbes are very rare. It is important to explicitly state the prospect of bacteriocin-producing microbes in prevention of gastrointestinal infection towards their application in host. This review discusses the potential of gut as an appropriate resource for mining targeted bacteriocin-producing microbes. Then, host-related factors affecting the bacteriocin production and activity of bacteriocin-producing microbes in the gut are summarized. Accordingly, the multiple mechanisms (direct inhibition and indirect inhibition) behind the preventive effects of bacteriocin-producing microbes on gut infection are discussed. Finally, we propose several targeted strategies for the manipulation of bacteriocin-producing beneficial microbes to improve their performance in antimicrobial outcomes. We anticipate an upcoming emergence of developments and applications of bacteriocin-producing beneficial microbes as antimicrobial agent in gut infection induced by pathogenic bacteria.

Iruplinalkib (WX-0593) Versus Crizotinib in ALK TKI-Naive Locally Advanced or Metastatic ALK-Positive NSCLC: Interim Analysis of a Randomized, Open-Label, Phase 3 Study (INSPIRE).

INTRODUCTION: Iruplinalkib (WX-0593) is a new-generation, potent ALK tyrosine kinase inhibitor (TKI) that has been found to have systemic and central nervous system (CNS) efficacy in ALK-positive NSCLC. We compared the efficacy and safety of iruplinalkib with crizotinib in patients with ALK TKI-naive, locally advanced or metastatic ALK-positive NSCLC. METHODS: In this open-label, randomized, multicenter, phase 3 study, patients with ALK-positive NSCLC were randomly assigned to receive iruplinalkib 180 mg once daily (7-d run-in at 60 mg once daily) or crizotinib 250 mg twice daily. The primary end point was progression-free survival (PFS) assessed by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included PFS by investigator, objective response rate (ORR), time to response, duration of response, intracranial ORR and time to CNS progression by IRC and investigator, overall survival, and safety. An interim analysis was planned after approximately 70% (134 events) of all 192 expected PFS events assessed by IRC were observed. Efficacy was analyzed in the intention-to-treat population. Safety was assessed in the safety population, which included all randomized patients who received at least one dose of the study drugs. This study is registered with Center for Drug Evaluation of China National Medical Products Administration (CTR20191231) and Clinicaltrials.gov (NCT04632758). RESULTS: From September 4, 2019, to December 2, 2020, a total of 292 patients were randomized and treated; 143 with iruplinalkib and 149 with crizotinib. At this interim analysis (145 events), the median follow-up time was 26.7 months (range: 3.7-37.7) in the iruplinalkib group and 25.9 months (range: 0.5-35.9) in the crizotinib group. The PFS assessed by IRC was significantly longer among patients in the iruplinalkib group (median PFS, 27.7 mo [95% confidence interval (CI): 26.3-not estimable] versus 14.6 mo [95% CI: 11.1-16.5] in the crizotinib group; hazard ratio, 0.34 [98.02% CI: 0.23-0.52], p < 0.0001). The ORR assessed by IRC was 93.0% (95% CI: 87.5-96.6) in the iruplinalkib group and 89.3% (95% CI: 83.1-93.7) in the crizotinib group. The intracranial ORR was 90.9% (10 of 11, 95% CI: 58.7-99.8) in the iruplinalkib group and 60.0% (nine of 15, 95% CI: 32.3-83.7) in the crizotinib group for patients with measurable baseline CNS metastases. Incidence of grade 3 or 4 treatment-related adverse events was 51.7% in the iruplinalkib group and 49.7% in the crizotinib group. CONCLUSIONS: Iruplinalkib was found to have significantly improved PFS and improved intracranial antitumor activity versus crizotinib. Iruplinalkib may be a new treatment option for patients with advanced ALK-positive and ALK TKI-naive NSCLC. FUNDING: This study was funded by Qilu Pharmaceutical Co., Ltd., Jinan, People's Republic of China, and partly supported by the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Continual Reinforcement Learning for Quadruped Robot Locomotion.

The ability to learn continuously is crucial for a robot to achieve a high level of intelligence and autonomy. In this paper, we consider continual reinforcement learning (RL) for quadruped robots, which includes the ability to continuously learn sub-sequential tasks (plasticity) and maintain performance on previous tasks (stability). The policy obtained by the proposed method enables robots to learn multiple tasks sequentially, while overcoming both catastrophic forgetting and loss of plasticity. At the same time, it achieves the above goals with as little modification to the original RL learning process as possible. The proposed method uses the Piggyback algorithm to select protected parameters for each task, and reinitializes the unused parameters to increase plasticity. Meanwhile, we encourage the policy network exploring by encouraging the entropy of the soft network of the policy network. Our experiments show that traditional continual learning algorithms cannot perform well on robot locomotion problems, and our algorithm is more stable and less disruptive to the RL training progress. Several robot locomotion experiments validate the effectiveness of our method.

Quorum-sensing gene regulates hormetic effects induced by sulfonamides in Comamonadaceae.

IMPORTANCE: Antibiotics can induce dose-dependent hormetic effects on bacterial cell proliferation, i.e., low-dose stimulation and high-dose inhibition. However, the underlying molecular basis has yet to be clarified. Here, we showed that sulfonamides play dual roles as a weapon and signal against Comamonas testosteroni that can modulate cell physiology and phenotype. Subsequently, through investigating the hormesis mechanism, we proposed a comprehensive regulatory pathway for the hormetic effects of Comamonas testosteroni low-level sulfonamides and determined the generality of the observed regulatory model in the Comamonadaceae family. Considering the prevalence of Comamonadaceae in human guts and environmental ecosystems, we provide critical insights into the health and ecological effects of antibiotics.

Super-fast Charging Biohybrid Batteries through a Power-to-formate-to-bioelectricity Process by Combining Microbial Electrochemistry and CO2 Electrolysis.

Extensive study on renewable energy storage has been sparked by the growing worries regarding global warming. In this study, incorporating the latest advancements in microbial electrochemistry and electrochemical CO2 reduction, a super-fast charging biohybrid battery was introduced by using pure formic acid as an energy carrier. CO2 electrolyser with a slim-catholyte layer and a solid electrolyte layer was built, which made it possible to use affordable anion exchange membranes and electrocatalysts that are readily accessible. The biohybrid battery only required a 3-minute charging to accomplish an astounding 25-hour discharging phase. In the power-to-formate-to-bioelectricity process, bioconversion played a vital role in restricting both the overall Faradaic efficiency and Energy efficiency. The CO2 electrolyser was able to operate continuously for an impressive total duration of 164 hours under Gas Stand-By model, by storing N2 gas in the extraction chamber during stand-by periods. Additionally, the electric signal generated during the discharging phase was utilized for monitoring water biotoxicity. Functional genes related to formate metabolism were identified in the bioanode and electrochemically active bacteria were discovered. On the other hand, Paracoccus was predominantly found in the used air cathode. These results advance our current knowledge of exploiting biohybrid technology.

Is it true that negative emotions cause more utilitarian judgements? from the influence of emotion and cognition.

ABSTRACTThe affect-as-information (AAI) model proposes that emotions influence the accessibility and value of information (Avramova & Inbar, 2013). Furthermore, according to the dual-process model of moral judgement, emotions and cognition influence moral judgement (Greene, 2007; Greene et al., 2001, 2008); however, there is no direct evidence of a causal chain to support this model's proposition. By using a 3 (emotions: positive vs. neutral vs. negative) × 2 (primed rule: save lives vs. do not kill) between-participants design, we examined two hypotheses in two experiments: supraliminal (Experiment 1) and subliminal (Experiment 2) priming. Our results partially supported the AAI model and confirmed that emotions and cognition independently influence moral judgement. Specifically, the positive emotions group made more utilitarian decisions after being primed with the "save lives" rule and more deontological decisions after being primed with the do not kill rule. However, priming did not affect moral judgement in the negative emotion condition. Further, irrespective of whether priming was done, the negative emotion group mostly made utilitarian decisions. Accordingly, we propose a dynamic dual-process model of moral judgement, that can help clarify how emotion and cognition influence moral judgement.

Structural Health Monitoring in Long-Span Steel Structures Based on the BeiDou Navigation Satellite System.

The BeiDou navigation satellite system (BDS) provides precise positioning, navigation, and timing (PNT) services in the Asia-Pacific Region, but the BDS-based structural health monitoring (SHM) approach (SHM) is rarely studied, especially in civil engineering. Moreover, how BDS can be applied to complete the tasks of SHM in a real project is also not fully investigated, especially working in conjunction with other techniques. This study aims to propose a BDS-based approach for SHM in civil engineering. The performance of the proposed approach is investigated through a case study-the Tianhan Grand Theater (TGT). A specific Tianhan system corresponding to BDS is proposed to complete the SHM tasks of TGT. Based on the collected data, the trusses with maximum displacement and stress are found by BDS to evaluate structural health in the construction stage. The results show that the maximum displacement and stress have certain safety reserves and meet the requirements of the specifications and regulations. Thus, BDS can satisfactorily complete the tasks of SHM for Long-span steel structures. This study gives a clear view to engineers and researchers that how to apply BDS in structural construction and provides a valuable real case for evaluating the performance of BDS in SHM.

Pembrolizumab plus chemotherapy for advanced non-small-cell lung cancer without tumor PD-L1 expression in Asia.

Aim: We pooled patient-level data from three randomized controlled studies to evaluate the combination of pembrolizumab plus chemotherapy in patients with untreated advanced/metastatic non-small-cell lung cancer (NSCLC) and programmed cell death ligand 1 (PD-L1) tumor proportion score <1% in East Asia. Methods: The analysis included 107 patients from China, Japan, Korea, Thailand and Taiwan (pembrolizumab plus chemotherapy, n = 56; chemotherapy alone, n = 51). Results: For pembrolizumab plus chemotherapy versus chemotherapy alone, median overall survival was 21.3 versus 12.6 months (HR, 0.55 [95% CI: 0.35-0.87]) and median progression-free survival was 8.4 versus 6.0 months (HR, 0.64 [95% CI: 0.43-0.96]). Conclusion: The analysis supports the use of pembrolizumab in combination with platinum-based chemotherapy for East Asian patients with PD-L1-negative, advanced NSCLC.

This analysis evaluated outcomes for East Asian patients with a type of advanced lung cancer which does not express a protein called programmed cell death ligand 1 (PD-L1). The patients received either an immunotherapy, called pembrolizumab, in combination with chemotherapy or chemotherapy alone. Overall survival (how long people live) and progression-free survival (how long people live without their disease getting worse) were longer for patients who received treatment with pembrolizumab plus chemotherapy versus those who received chemotherapy alone. Side effects among East Asian patients were similar to those previously described for a global patient population. These results support the use of pembrolizumab in combination with chemotherapy for East Asian patients with lung cancer that does not express PD-L1. Clinical Trial Registration: NCT02039674; NCT02578680; NCT03950674; NCT02775435; NCT03875092 (ClinicalTrials.gov).

Bidirectional Synaptic Phototransistor Based on Two-Dimensional Ferroelectric Semiconductor for Mixed Color Pattern Recognition.

Optoelectronic synaptic devices capable of processing multiwavelength inputs are critical for neuromorphic vision hardware, which remains an important challenge. Here, we develop a bidirectional synaptic phototransistor based on a two-dimensional ferroelectric semiconductor of α-In2Se3, which exhibits bidirectional potentiated and depressed synaptic weight update under optical pulse stimulation. Importantly, the bidirectional optoelectronic synaptic behavior can be extended to multiwavelengths (blue, green, and red light), which could be used for color recognition. The mechanism underlying the bidirectional synaptic characteristics is attributed to the gate-configurable barrier heights as revealed by the Kelvin probe force microscopy measurement. The α-In2Se3 device exhibits versatile synaptic plasticity such as paired-pulse facilitation, short- and long-term potentiation, and long-term depression. The bidirectional optoelectronic synaptic weight updates under multiwavelength inputs enable a high accuracy of 97% for mixed color pattern recognition.

Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here. METHODS: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated. RESULTS: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were -52.0% (range: -100.0 to 16.1%) and -46.8% (95% CI: -55.5 to -38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months. CONCLUSIONS: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

Enhancement of micropollutant biotransformation by adding manganese sand in constructed wetlands.

Recent investigations have shown that the addition of manganese (Mn) sand to constructed wetlands (i.e., Mn-amended CWs) can improve the performance of organic micropollutants (MPs) removal. In addition to the direct oxidation and adsorption of Mn oxides, the indirect role of Mn oxides in MP biotransformation is crucial to the removal of MPs but has seldom been referred to. Herein, we constructed lab-scale CWs with or without the addition of natural Mn sand (∼35% Mn oxides) to decipher the influence of Mn oxides on the biotransformation of the six selected MPs which commonly existed in the wastewater. The experimental results showed that the addition of Mn sand to CWs can improve the removal of MPs (8.48% atrazine, 13.16% atenolol, and 6.27% sulfamethoxazole [pairwise Wilcoxon test p < 0.05]). Combining the detection of transformation products and metagenomic sequencing, we found that the enhanced removal of atrazine in the Mn-amended CWs was mainly due to the bioaugmented hydroxylation process. The enrichment of biotransformation-related genes and associated microbes of atenolol and sulfamethoxazole in Mn-amended CWs indicated that the addition of Mn sand to CWs can strengthen the biotransformation of MPs. Furthermore, we found that these MP-biodegrading microbes were widely present in the full-scale CWs. Overall, our research provides fundamental information and insights for further application of Mn-amended CWs in MP removal.

Electricity-Driven Microbial Metabolism of Carbon and Nitrogen: A Waste-to-Resource Solution.

Electricity-driven microbial metabolism relies on the extracellular electron transfer (EET) process between microbes and electrodes and provides promise for resource recovery from wastewater and industrial discharges. Over the past decades, tremendous efforts have been dedicated to designing electrocatalysts and microbes, as well as hybrid systems to push this approach toward industrial adoption. This paper summarizes these advances in order to facilitate a better understanding of electricity-driven microbial metabolism as a sustainable waste-to-resource solution. Quantitative comparisons of microbial electrosynthesis and abiotic electrosynthesis are made, and the strategy of electrocatalyst-assisted microbial electrosynthesis is critically discussed. Nitrogen recovery processes including microbial electrochemical N2 fixation, electrocatalytic N2 reduction, dissimilatory nitrate reduction to ammonium (DNRA), and abiotic electrochemical nitrate reduction to ammonia (Abio-NRA) are systematically reviewed. Furthermore, the synchronous metabolism of carbon and nitrogen using hybrid inorganic-biological systems is discussed, including advanced physicochemical, microbial, and electrochemical characterizations involved in this field. Finally, perspectives for future trends are presented. The paper provides valuable insights on the potential contribution of electricity-driven microbial valorization of waste carbon and nitrogen toward a green and sustainable society.

CHARACTERIZATION OF MACULAR NEOVASCULARIZATION IN BIETTI CRYSTALLINE DYSTROPHY USING MULTIMODAL IMAGING MODALITIES.

PURPOSE: To characterize the clinical features of macular neovascularization (MNV) secondary to Bietti crystalline dystrophy. METHODS: The imaging data of 157 eyes in 79 patients with Bietti crystalline dystrophy were retrospectively reviewed. 12 individuals (19 eyes) were found to have MNVs. Multimodal retinal imaging was used to evaluate the features of MNVs and the primary chorioretinopathy. RESULTS: The MNV lesions were shown as typical type 2 MNVs with subretinal hyperreflective material (SHRM), and usually detected along the borders of the retinal pigment epithelium/choriocapillaris dropout. The active MNVs were noted in earlier stages of Bietti crystalline dystrophy, while the activity was observed to be reduced in advanced cases. On spectral domain optical coherence tomography, the outer retinal structures were demonstrated to be partially preserved above the SHRMs compared with the extensive atrophy contiguously. Fibrotic scaring of the MNVs was commonly observed and arteriolarization was usually shown within the scars. CONCLUSION: MNV was demonstrated to be a common complication secondary to Bietti crystalline dystrophy. The lesions were typical type 2 MNV of varied activities possibly associated with the degrees of the primary degeneration. Choriocapillaris hypoperfusion may participate in MNV development.

HIF1α and HIF2α regulate non-small-cell lung cancer dedifferentiation via expression of Sox2 and Oct4 under hypoxic conditions.

OBJECTIVE: To explore HIF1α and HIF2α regulate the dedifferentiation of lung cancer cells under hypoxic conditions through Sox2 and Oct4. MATERIALS AND METHODS: HIF1α, HIF2α, Sox2 and Oct4 expression was analysed in lung cancer tissues. We analysed sphere formation by single-cell of differentiated lung cancer under hypoxia, and detected the expression of CD133, CD44, Sox2, Oct4, HIF1α and HIF2α. We knocked out HIF1α, HIF2α, Sox2 or Oct4 in cells, cultured the cells under hypoxic conditions and detected CD133 and CD44 using western blotting. We also detected the apoptosis rate of cells with HIF1α, HIF2α, Sox2 or Oct4 knockout. RESULTS: There was more sphere formation of differentiated lung cancer cells under hypoxic conditions than of control cells under normoxic conditions. These newly formed spheres highly expressed CD133 and CD44. TCGA database showed high expression of HIF1α and HIF2α in lung cancer tissues. After knocking out HIF1α and HIF2α, the expression of Sox2, Oct4, CD133 and CD44 decreased significantly, and after knocking out Sox2 or Oct4, the expression of CD133 and CD44 decreased. CONCLUSION: HIF1α and HIF2α regulate non-small-cell lung cancer dedifferentiation through Sox2 and Oct4 under hypoxic conditions.

Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This phase IIa study was part of a phase I/IIa study (NCT03386955), aimed to evaluate the efficacy and safety of rezivertinib as the first-line treatment for patients with locally advanced or metastatic/recurrent EGFR mutated non-small cell lung cancer (NSCLC). METHODS: Patients received the first-line treatment of 180 mg rezivertinib orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: From Jun 12, 2019, to Oct 17, 2019, 43 patients were enrolled. At the data cutoff date on Dec 23, 2021, the ORR by BICR was 83.7% (95% CI: 69.3-93.2%). The median DoR was 19.3 (95% CI: 15.8-25.0) months. The median PFS by BICR was 20.7 (95% CI: 13.8-24.8) months and 22.0 (95% CI: 16.8-26.3) months by investigators. Data on OS was immature. Totally, 40 (93.0%) patients had at least one treatment-related adverse event while 4 (9.3%) of them were grade ≥ 3. CONCLUSIONS: Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03386955.

Dam construction alters planktonic microbial predator‒prey communities in the urban reaches of the Yangtze River.

While dam construction supports social and economic development, changes in hydraulic conditions can also affect natural aquatic ecosystems, especially microbial ecosystems. The compositional and functional traits of multi-trophic microbiota can be altered by dam construction, which may result in changes in aquatic predator-prey interactions. To understand this process, we performed a large-scale sampling campaign in the urban reaches of the dam-impacted Yangtze River (1 995 km) and obtained 211 metagenomic datasets and water quality data. We first compared the compositional traits of planktonic microbial communities upstream, downstream, and in a dam reservoir. Results showed that Bacteroidetes (R-strategy) bacteria were more likely to survive upstream, whilst the reservoir and downstream regions were more conducive to the survival of K-strategy bacteria such as Actinobacteria. Eukaryotic predators tended to be enriched upstream, whilst phototrophs tended to be enriched in the reservoir and downstream regions. Based on bipartite networks, we inferred that the potential microbial predator-prey interactions gradually and significantly decreased from upstream to the downstream and dam regions, affecting 56% of keystone microbial species. Remarkably, functional analysis showed that the abundance of the photosynthetic gene psbO was higher in the reservoir and downstream regions, whilst the abundance of the KEGG carbohydrate metabolic pathway was higher upstream. These results indicate that dam construction in the Yangtze River induced planktonic microbial ecosystem transformation from detritus-based food webs to autotroph-based food webs.