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Abstract Solving the problem of gas extraction from low-permeability coal seams is an urgent issue in the global coal industry, and exploring green and efficient mining methods has potential applications in this field. In this study, the No. 9 coal seam of the Guizhou Longfeng Coal Mine was selected as the research object. The method of using a hydraulic horizontal slit to create a compensation space and then synergizing it with the coal body’s own stress to decompress and increase the permeability of the coal body was studied through similarity simulation and numerical simulation experiments. This study showed that the slit can cause the overall development, expansion, and penetration of coal seam fissures. Thereby, a large number of fissures are produced in the coal seam and its upper rock layer, which form, as a whole, a “positive trapezoid” shape. The three stages of the slit produced 165, 487, and 1572 fissures, which unpressurized and increased the penetration of the coal and rock body. The slit causes the upper coal body to lose its support, and the original stress balance of the coal and rock is broken, forming a decompression zone. At the same time, the coal body below starts to expand and deform after losing the vertical stress. The decompression zone gradually expands up and down, and the stress on both ends of the compensation space becomes larger, forming a stress concentration area. After the overall displacement of the coal seam caused by the slit, a “positive triangle” area is formed. In the upper part of the area, six displacement dividing lines are created, which form five areas. The displacement shows the distribution characteristics of a large displacement in the middle and a small displacement at both ends. The results of the similarity simulation and numerical simulation experiments were verified. The study provides a new way of thinking for effectively preventing coal and gas protrusion and improving mining efficiency.

Abstract Oncogenic RET alteration is an important, tissue-agnostic therapeutic target across diverse cancers. We conducted a first-in-human phase 1 study on SY-5007, a potent and selective RET inhibitor, in patients with RET-altered solid tumors. Primary endpoints were safety, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D). Secondary endpoints included pharmacokinetics and preliminary anti-tumor activity. A total of 122 patients were enrolled (17 in dose-escalation phase and 105 in dose-expansion phase), including 91 with non-small cell lung cancer, 23 with medullary thyroid cancer, 7 with papillary thyroid cancer and 1 with gastric cancer. Treatment-related adverse events (TRAEs) were reported in 96.7% of patients, with the most common grade ≥ 3 TRAEs being hypertension (22.1%), diarrhea (16.4%), hypertriglyceridemia (6.6%), and neutropenia (6.6%). The exposure to SY-5007 was dose proportional. Among the 116 efficacy-evaluable patients, the overall objective response rate (ORR) was 57.8%, with 70.0% in treatment-naïve patients and 51.3% in previously treated patients. The median progression-free survival (PFS) was 21.1 months. Efficacy was observed regardless of tumor types and previous therapies. Biomarker analysis of 61 patients with circulating tumor DNA (ctDNA)-detectable RET alterations showed an ORR of 57.4% and median PFS of 13.8 months. Rapid ctDNA clearance of RET alteration correlated with faster responses and improved outcomes. In relapsed patients, off-target induced resistance was observed in 57.1% (12/21), with no on-target RET alterations identified. In conclusion, SY-5007 was well-tolerated and showed promising efficacy in patients with RET-altered solid tumors. Serial ctDNA monitoring may unveil treatment response and potential resistance mechanisms (NCT05278364).

Abstract Aims: Straw turnover plays an important role in reducing soil diseases, improving the ecological environment of plowland and realizing the effective ecological utilization of straw. Methods: Pot and field experiments were carried out to investigate the effects of maize, rice and wheat straws on the growth, clubroot disease of Chinese cabbage and soil nutrients. Undecomposed and decomposed maize, rice and wheat straws were quantitatively added to the monocultural soil of Chinese cabbage, and the crops without straw were taken as the control. Results: The results showed that the addition of maize, wheat and rice straws could promote the growth of monocultural Chinese cabbage, inhibit the occurrence of clubroot disease, increase soil pH value, the content of soil organic matter, alkaline hydrolyzable nitrogen and available potassium in pot experiment. Exogenous straw application could reduce the incidence rate by 22.54 ~ 47.85%, increase the plot yield of field 95.15 ~ 365.81%. Conclusions: In terms of inhibiting clubroot disease and improving soil properties, undecomposed rice straw is superior to maize and wheat straw, while decomposed maize straw is superior to rice and wheat straw.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract. Background:. Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women. Methods:. Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension. Results:. Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women (Pfor trend

Background: Currently, awareness about platelet count (PC) and its consequences for perinatal outcome have increased, but there is little reliable evidence on fecundability. Methods: Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 5,524,886 couples met the inclusion criteria and were included in this cohort study. Cox regression models were adopted to estimate fecundability ratios (FRs) and their 95% confidence intervals (CIs) for pre-pregnancy PC quintiles. Restricted cubic splines were used to flexibly model and visualize the relationship of PC with FRs. Microsoft SQL server and R software were used for data management and analysis. Results: The median of pre-pregnancy PC among women was 221.00 × 109/L. The first (223.06 × 109/L) were associated with the risk of reduced female fecundability (P for non-linearity < 0.01). Conclusion: PC is associated with female fecundability. Further classification of PC levels may deepen our understanding of the early warnings and significance of female fecundability.

Henan encountered a multi-stage severe convective weather event (hereinafter referred to as "6.13" event) accompanied by local tornado on 13 June 2022. Using conventional observation data, regional automatic weather station data, satellite cloud images, Doppler weather radar data, ERA5 reanalysis data and other relevant data, we conducted an analysis on atmospheric circulation environment and the evolution characteristics of mesoscale systems for the "6.13" event. In addition, we discussed the initiation and maintenance mechanisms of convection in the different periods of this event and the radar characteristics of the local tornado in Puyang of Henan. Results are as follows. (1) The "6.13" event occurs under the northwest airflow behind the northeast cold vortex trough, and it is characterized by wide impact range, long duration and multiple types of disaster weather. (2) Radar detection results show that the severe convective systems in the "6.13" event passed through Henan in three periods one after another, and strong echoes in each period lasts for 8-9 hours, with the moving speed of 30-50 km·h-1. Most of the severe convective systems are multi-cells that all moved from northwest to southeast, with some of their areas overlapping under the guidance of northwest airflow. (3) Maintenance of the strong conditional instability and the moderate to strong vertical wind shear over Henan is an important cause for multi-stage severe convective weather in the "6.13" event lasting for a long time. The first period of local severe convection in Henan is mainly triggered by the convergence line or convergence center in the boundary layer formed by the combined effect of daily changes of wind field, local cold air activity, topographic distribution, while the second and third periods of severe convection are triggered by the gust front or outflow boundary accompanied by the surface mesoscale thunderstorm high formed by the strong developing convection systems in the surrounding area in the previous period or the same period. (4) The local tornado in Puyang is generated by a rapidly developing supercell storm. The hook echo and mesoscale cyclonic vortex appear 12 minutes after this supercell storm, and the tornado vortex characteristics (TVS) appear 18 minutes later. The hook echo and mesoscale cyclonic vortex are 6 minutes ahead of the occurrence of tornado, which can provide a reference information for early warning local tornadoes.

With the impact of global climate change and the urbanization process, the risk of urban flooding has increased rapidly, especially in developing countries. Real-time monitoring and prediction of flooding extent and drainage system are the foundation of effective urban flood emergency management. Therefore, this paper presents a rapid nowcasting prediction method of urban flooding based on data-driven and real-time monitoring. The proposed method firstly adopts a small number of monitoring points to deduce the urban global real-time water level based on a machine learning algorithm. Then, a data-driven method is developed to achieve dynamic urban flooding nowcasting prediction with real-time monitoring data and high-accuracy precipitation prediction. The results show that the average MAE and RMSE of the urban flooding and conduit system in the deduction method for water level are 0.101 and 0.144, 0.124 and 0.162, respectively, while the flooding depth deduction is more stable compared to the conduit system by probabilistic statistical analysis. Moreover, the urban flooding nowcasting method can accurately predict the flooding depth, and the R2 are as high as 0.973 and 0.962 of testing. The urban flooding nowcasting prediction method provides technical support for emergency flood risk management. HIGHLIGHTS A rapid nowcasting prediction method of urban flood based on data-driven and real-time monitoring.; The deduction model accurately estimates the global water depth.; The proposed urban flooding nowcasting model was observed to outperform the traditional machine learning model to predict.;

Probiotics have a variety of probiotic effects. However, in the process of processing, storage or digestion, it is easy to reduce its activity due to the influence of external adverse environment. The use of microcapsule technology can play a good role in the protection of probiotics and reduce or avoid the impact of adverse environment. As a wall material of probiotic microcapsules, marine polysaccharides can not only boost the stress resistance and stability of probiotics, improve the sensory characteristics of probiotic products, but also enhance the therapeutic effect with probiotics. This paper analyzes the species and characteristics of marine polysaccharides from different sources. It also summarizes the preparation methods of marine polysaccharide-based probiotic microcapsules, and expounds the application of marine polysaccharide-based probiotic microcapsules in food industry, biomedicine, aquaculture feed and other fields. It is expected to provide some references for the research direction of probiotic microcapsules and the high-value utilization of marine resources.

ObjectiveNeuroendoscopic surgery (NES) has been proven to be safe and effective in hematoma evacuation for cerebral hemorrhage. However, its efficacy for thalamic hemorrhage accompanied by intraventricular hematoma (THAVH) remains unclear. The aim of this study is to determine the efficacy of NES in treating THAVH.MethodA retrospective study was carried out. The data of patients diagnosed with THAVH were collected from January 1st, 2019, to January 1st, 2022. Patients received the NES or external ventricle drainage (EVD) treatment were assigned to the NES or EVD group, respectively. As primary outcomes, the hematoma evacuation volume, residual hematoma volume, and hematoma clearance rate were separately calculated based on the hematoma site; and the 180-day-mRS score was assessed. As secondary outcomes, the length of stay in the ICU and hospital, and the adverse events were also compared.ResultsThirty-five patients, aged 66.37 ± 6.62 years, were in the NES group; and 40 patients, aged 68.75 ± 7.22 years, were in the EVD group. The baseline characteristics in the two groups were similar (P > 0.05). The gross hematoma evacuation volume, volume of hematoma evacuated in the thalamus or the ventricle, and the hematoma clearance rate were greater in the NES group than in the EVD group on the 1st day after surgery (P 3, the mean residual hematoma volume in the thalamus of patients with mRS ≤3 on the 1st and 7th day were less in each group (P 3 in the EVD group on the 1st day after surgery (P

Alzheimer's disease (AD) is a gradual neurodegenerative ailment that lacks any disease-modifying intervention. Our objective was to pinpoint pharmacological targets with a focus on amyloid beta (Aβ) and tau to treat and prevent AD in the European population. A proteome-wide Mendelian randomization (MR) analysis was carried out to estimate the associations between proteins and cerebrospinal fluid (CSF) Aβ-42 and phosphorylated Tau (p-Tau). We utilized colocalization and MR analysis to investigate whether the identified proteins were associated with the risk of AD. Additionally, we expanded our investigation to include non-AD phenotypes by conducting a phenome-wide MR analysis of 1646 disease traits based on the FinnGen and UK Biobank databases to explore potential side effects. We identified 11 proteins that were genetically associated with both CSF Aβ-42 and p-Tau levels. The genetically predicted levels of three proteins, GAL3ST2, POLR1C, and BIN1, were found to be associated with an increased risk of AD with high colocalization. In the phenome-wide MR analysis, two out of the three biomarkers were associated with at least one disease, except for GAL3ST2, which was not associated with any disease under the threshold of FDR

Study region: The Ailaoshan National Nature Reserve forest is a mountainous water catchment area for the Lancang River basin and a subtropical ecological conservation area in southwest China. Study focus: The study aimed to understand how water fluxes in a subtropical forest responds to extreme weather disturbances and their recoveries in the post-damage years. We used eddy covariance data (2010–2019) to investigate the evapotranspiration (ET), transpiration (T), evaporation (E), and canopy conductance (Gc) before and after an extreme snow event in 2015. New Hydrological Insights: In the snow damage year, the leaf area index (LAI) decreased by 49 % compared to the pre-damage levels. The severe vegetation damage caused a significant decrease in ET, T, E, and Gc by 35 %, 36 %, 23 %, and 33 %, respectively, compared to the pre-damage levels. T returned to its pre-damage level in 2016, one year after the snow damage. In contrast, LAI, ET, E and Gc recovered to their pre-damage levels in 2018, four years after the initial damage. Reduced ET caused a strong positive RFET, which diminished forest evaporative cooling and resilience. Our results suggest that the delayed E recovery enables water reserves in the ecosystems to be used through T to support rapid understory vegetation growth. This mechanism plays critical in bolstering ecosystem resilience as it facilitates swift recovery following disturbances in subtropical forests.

Introduction: Previous results from the phase 3 ALESIA study (NCT02838420) revealed that alectinib (a central nervous system [CNS]-active, ALK inhibitor) had clinical benefits in treatment-naïve Asian patients with advanced ALK-positive NSCLC, consistent with the global ALEX study. We present updated data after more than or equal to 5 years of follow-up from the “last patient in” date. Methods: Adult patients with treatment-naïve, advanced ALK-positive NSCLC from mainland China, South Korea, and Thailand were randomized 2:1 to receive twice-daily 600 mg alectinib (n = 125) or 250 mg crizotinib (n = 62). The primary endpoint was investigator-assessed progression-free survival. Secondary or exploratory endpoints included overall survival, objective response rate, time to CNS progression, and safety. Results: At the data cutoff (May 16, 2022), the median survival follow-up was 61 and 51 months in the alectinib and crizotinib arms, respectively. Median progression-free survival was 41.6 months with alectinib versus 11.1 months with crizotinib (stratified hazard ratio = 0.33, 95% confidence interval: 0.23–0.49). Overall survival data remain immature; 5-year overall survival rates were 66.4% (alectinib arm) versus 56.1% (crizotinib arm). Objective response rate was 91.2% versus 77.4% with alectinib and crizotinib, respectively. CNS progression was delayed with alectinib versus crizotinib (cause-specific hazard ratio = 0.16, 95% confidence interval: 0.08–0.32). Median treatment duration was longer with alectinib versus crizotinib (42.3 versus 12.6 mo). No new safety signals were observed. Conclusions: With four additional years of follow-up, these updated results confirm the clinical benefit and manageable safety of alectinib in Asian patients with advanced ALK-positive NSCLC, and confirm alectinib as a standard-of-care treatment for patients with advanced ALK-positive NSCLC.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract Natural language processing techniques enable extraction of valuable information from large amounts of published literature for the application of data science and technology, i.e. machine learning in the field of materials science. Nevertheless, the automated extraction of data from full-text documents remains a complex task. We propose a document-level natural language processing pipeline for literature extraction of comprehensive information on layered cathode materials for sodium-ion batteries. The pipeline enhances entity recognition with contextual supplementary information while capturing the article structure. Finally, a heuristic multi-level relationship extraction algorithm is employed in relation extraction to extract experimental parameters and complex performance relationships respectively. We successfully extracted a comprehensive dataset containing 5265 records from 1747 documents, encompassing essential information such as chemical composition, synthesis parameters, and electrochemical properties. By implementing our pipeline, we have made significant progress in overcoming the challenges associated with data scarcity in battery informatics. The extracted datasets provide a valuable resource for further research and development in the field of layered cathode materials.

Abstract For shaped charge blasting projects in mining, civil engineering, and similar fields, it is proposed to modify the charge structure by combining slotted tubes and shaped charge liners to obtain a new type of charge structure. This aims to achieve directional rock breaking through the focused action of the shaped charge. The influence of different slotted pipe materials on the directional rock-breaking effect of concentrated energy using a new charge structure is explored through theoretical analysis combined with model test study, high-speed camera, stress–strain gauge, and other equipment. A comparison is made between slotted pipes made of aluminum, kraft paper, and PVC, with the cutting width of 2 mm. Based on the characteristics of the cracks formed after blasting, the new charge structure made of aluminum slotted pipe produces a penetrating crack that is almost consistent with the pre-cracking direction. Based on the corresponding characteristics of successively released blasting energy, the guiding and convergence effect of the new charge structure made of aluminum slotted pipe on the explosion energy is greater than that of the new charge structure made of the other two types of slotted pipe material. According to the strain data measured after blasting, the peak arrival time of the strain peak in the direction of the slotted pipe on one side of the shaped hood is shorter than that in the other two directions, and the peak strain is greater than that in the other two directions while having a better energy gathering effect. Based on the findings, the new charge structure with directional energy concentration has a damage reduction effect. Furthermore, the material of aluminum slotted pipe is found to be better than PVC slotted pipe, whereas the material of PVC slotted pipe is better than kraft paper slotted pipe in achieving directional rock breaking.

Objective: To investigate the relationship between ambient fine particulate matter (PM2.5) exposure and fecundability. Methods: This study included 751,270 female residents from Henan Province who participated in the National Free Pre-conception Check-up Projects during 2015–2017. Ambient cycle-specific PM2.5 exposure was assessed at the county level for each participant using satellite-based PM2.5 concentration data at 1-km resolution. Cox proportional hazards models with time-varying exposure were used to estimate the association between fecundability and PM2.5 exposure, adjusted for potential individual risk factors. Results: During the study period, 568,713 participants were pregnant, monthly mean PM2.5 concentrations varied from 25.5 to 114.0 µg/m3 across study areas. For each 10 µg/m3 increase in cycle-specific PM2.5, the hazard ratio for fecundability was 0.951 (95 % confidence interval: 0.950–0.953). The association was more pronounced in women who were older, with urban household registration, history of pregnancy, higher body mass index (BMI), hypertension, without exposure to tobacco, or whose male partners were older, with higher BMI, or hypertension. Conclusion: In this population-based prospective cohort, ambient cycle-specific PM2.5 exposure was associated with reduced fecundability. These findings may support the adverse implications of severe air pollution on reproductive health.

Abstract Background Folic acid supplementation is recommended for reducing the risk of birth defects. We aimed to assess the protective association of periconception folic acid supplements with birth defects in real-world setting. Methods This prospective, population-based cohort study utilized national preconception registered data of married Chinese couples planning a pregnancy within 6 months between 2010 and 2012 in Mainland China. Participated women are freely provided folic acid starting 3 months before conception till 3 months after conception. Birth defects were self-reported at 42 days postpartumn followup. R software (v4.0.2) was applied for statistical analyses. Results Complete data of 567,547 couples with pregnancy outcomes and folic acid supplementation were extracted for final analysis. A total of 74.7% women were with folic acid supplementation, and 599 birth defects were self-reported. The odd of birth defects was lower among women taking folic acid compared to their counterparts not taking (0.102% vs 0.116%, P

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Abstract Background The postponement of parenthood is a global public health issue that has received attention of many public health experts. However, few studies have investigated the postponement in marriage age, marriage and conception interval, and pregnancy age in terms of demographic and regional heterogenicities. Methods This is a cross-sectional, registry-based study, and a total of 13 894 601 nulliparous couples who participated in the National Free Pre-Pregnancy Check-ups Project and became pregnant during 2013–2019 were included. We calculated annual percentage change and forest plots for marriage age, marriage and conception interval, and pregnancy age. Results Late marriage (marriage age ≥ 35 years), long marriage and conception interval (marriage and conception interval ≥ 2 years), and advanced pregnancy (pregnancy age ≥ 35 years) increased from 1.20%, 22.01%, and 1.88% in 2013 to 1.69%, 32.75%, and 2.79% in 2019, respectively. The corresponding annual percentage changes were 6.55%, 8.44%, and 8.17%. Participants without higher education had a higher annual percentage change, but comparable prevalence for long marriage and conception interval with participants with higher education. Participants residing in second- or new first-tier cities, and the northeast of China who had a higher prevalence of parenthood postponement also had higher corresponding annual percentage changes. Conclusions Structural postponement of parenthood with demographic and regional heterogenicities was observed among Chinese nulliparous couples with planned pregnancies during 2013–2019. Inclusive and comprehensive parenting support should be developed and implemented in mainland China to minimize the negative health effects arising from the postponement, especially for couples without higher education and living in new first/second-tier cities or the northeast China.

Savannas are widespread biomes with highly valued ecosystem services. To successfully manage savannas in the future, it is critical to better understand the long-term dynamics of their productivity and phenology. However, accurate large-scale gross primary productivity (GPP) estimation remains challenging because of the high spatial and seasonal variations in savanna GPP. China’s savanna ecosystems constitute only a small part of the world’s savanna ecosystems and are ecologically fragile. However, studies on GPP and phenological changes, while closely related to climate change, remain scarce. Therefore, we simulated savanna ecosystem GPP via a satellite-based vegetation photosynthesis model (VPM) with fine-resolution harmonized Landsat and Sentinel-2 (HLS) imagery and derived savanna phenophases from phenocam images. From 2015 to 2018, we compared the GPP from HLS VPM (GPPHLS-VPM) simulations and that from Moderate-Resolution Imaging Spectroradiometer (MODIS) VPM simulations (GPPMODIS-VPM) with GPP estimates from an eddy covariance (EC) flux tower (GPPEC) in Yuanjiang, China. Moreover, the consistency of the savanna ecosystem GPP was validated for a conventional MODIS product (MOD17A2). This study clearly revealed the potential of the HLS VPM for estimating savanna GPP. Compared with the MODIS VPM, the HLS VPM yielded more accurate GPP estimates with lower root-mean-square errors (RMSEs) and slopes closer to 1:1. Specifically, the annual RMSE values for the HLS VPM were 1.54 (2015), 2.65 (2016), 2.64 (2017), and 1.80 (2018), whereas those for the MODIS VPM were 3.04, 3.10, 2.62, and 2.49, respectively. The HLS VPM slopes were 1.12, 1.80, 1.65, and 1.27, indicating better agreement with the EC data than the MODIS VPM slopes of 2.04, 2.51, 2.14, and 1.54, respectively. Moreover, HLS VPM suitably indicated GPP dynamics during all phenophases, especially during the autumn green-down period. As the first study that simulates GPP involving HLS VPM and compares satellite-based and EC flux observations of the GPP in Chinese savanna ecosystems, our study enables better exploration of the Chinese savanna ecosystem GPP during different phenophases and more effective savanna management and conservation worldwide.

Colorectal cancer (CRC) poses a significant global health challenge, ranking as the third most diagnosed cancer and the second leading cause of cancer-related deaths. Despite advancements in treatment, challenges such as delayed diagnosis, multidrug resistance, and limited therapeutic effectiveness persist, emphasizing the need for innovative approaches. This review explores the potential of natural products, nutraceuticals, and phytochemicals for targeting ferroptosis-related regulators as a novel strategy in CRC. Ferroptosis, a form of regulated cell death characterized by iron-dependent lethal lipid peroxide accumulation, holds substantial importance in CRC progression and therapy resistance. Natural products, known for their diverse bioactive effects and favorable safety profiles, emerge as promising candidates to induce ferroptosis in CRC cells. Exploring amino acid, iron, lipid metabolism regulators, and oxidative stress regulators reveals promising avenues for inducing cell death in CRC. This comprehensive review provides insights into the multifaceted effects of natural products on proteins integral to ferroptosis regulation, including GPX4, SLC7A11, ACSL4, NCOA4, and HO-1. By elucidating the intricate mechanisms through which natural products modulate these proteins, this review lays the foundation for a promising therapeutic strategy in CRC.

Abstract The inherent unpredictability of the maritime environment leads to low rates of survival during accidents. Life jackets serve as a crucial safety measure in underwater environments. Nonetheless, most conventional life jackets lack the capability to monitor the wearer's underwater body movements, impeding their effectiveness in rescue operations. Here, we present an intelligent self‐powered life jacket system (SPLJ) composed of a wireless body area sensing network, a set of deep learning analytics, and a human condition detection platform. Six coaxial core‐shell structure triboelectric fiber sensors with high sensitivity, stretchability, and flexibility are integrated into this system. Additionally, a portable integrated circuit module is incorporated into the SPLJ to facilitate real‐time monitoring of the wearer's movement. Moreover, by leveraging the deep‐learning‐assisted data analytics and establishing a robust correlation between the wearer's movements and condition, we have developed a comprehensive system for monitoring drowning individuals, achieving an outstanding recognition accuracy of 100%. This groundbreaking work introduces a fresh approach to underwater intelligent survival devices, offering promising prospects for advancing underwater smart wearable devices in rescue operations and the development of ocean industry.

Abstract The shape of a charge liner used in shaped charges with a combined liner will greatly influence the blasting effect. In this study, we examined how combined charge liners with different shapes affected directional rock blasting, and we assessed the influence mechanism. The numerical simulation results showed that among the three shaped charge liners, liners with arc and triangular shapes performed significantly better than the flat‐top liner, and the triangular liner was slightly superior to the arc‐shaped liner. Model testing indicated that principal cracks in the arc‐shaped and triangular liners developed along the combined energy‐gathering direction, while the principal cracks of the flat‐top liner deviated 32° from the axis. Therefore, the directional cracking effect of arc‐shaped and triangular liners was superior to the flat‐top liner. According to the peak strain values on the liners, the peak strain in the combined energy‐gathering direction was greater than that in the slot and nonenergy‐gathering directions, and the order of the peak strain of the three liners followed arc‐shaped liner > triangular liner > flat‐top liner. The directional blasting effect of the triangular liner was slightly better than the arc‐shaped liner. In conclusion, the findings of this study suggested that the best directional rock‐blasting effect was achieved when the shape of the combined charge liner was triangular.

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Abstract In order to study the influence of slit structure on the blasting effect of slit charge, the super dynamic strain test system and photographic equipment were used to study the dynamic response of slit charge blasting and the distribution of blasting cracks under different slit shapes and slit angles. The results show that changing the shape of the slit does not make the energy-gathering and damage-reducing blasting effect of the slit cartridge disappear, but it will affect its effect. Compared with the round hole slit, the peak strain in the slit direction of the strip slit cartridge blast is larger, the directional crack forming is more obvious, and the blasting effect is better. The energy accumulation and loss reduction effect of the blasting of the strip slotted cartridge increase first and then decrease with the increase of the slit angle. When the slit angle is 20°, the energy accumulation and loss reduction effect of strip slit charge blasting are the largest, the distribution of blasting cracks is the best, and the directional fracture blasting effect of slit charge is the best. Finally, based on the research results of model test, combined with the actual situation of the construction site, the slotted cartridge is applied to the pre-splitting blasting of open-pit slope. Compared with the ordinary cartridge pre-splitting blasting, the slope roughness after blasting is reduced by 46.2%, the half-hole rate of blast hole is increased by 20.5%, the blasting vibration intensity is reduced by 60.3%, and the directional fracture control blasting effect is good.

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

To improve probiotics’ survivability during gastrointestinal digestion and heat treatment, Lactobacillus plantarum was microencapsulated by spray-drying using Laminaria japonica polysaccharide/sodium caseinate/gelatin (LJP/SC/GE) composites. Thermogravimetry and differential scanning calorimetry results revealed that the denaturation of LJP/SC/GE microcapsules requires higher thermal energy than that of SC/GE microcapsules, and the addition of LJP may improve thermal stability. Zeta potential measurements indicated that, at low pH of the gastric fluid, the negatively charged LJP attracted the positively charged SC/GE, helping to maintain an intact microstructure without disintegration. The encapsulation efficiency of L. plantarum-loaded LJP/SC/GE microcapsules reached about 93.4%, and the survival rate was 46.9% in simulated gastric fluid (SGF) for 2 h and 96.0% in simulated intestinal fluid (SIF) for 2 h. In vitro release experiments showed that the LJP/SC/GE microcapsules could protect the viability of L. plantarum in SGF and release probiotics slowly in SIF. The cell survival of LJP/SC/GE microcapsules was significantly improved during the heat treatment compared to SC/GE microcapsules and free cells. LJP/SC/GE microcapsules can increase the survival of L. plantarum by maintaining the lactate dehydrogenase and Na+-K+-ATPase activity. Overall, this study demonstrates the great potential of LJP/SC/GE microcapsules to protect and deliver probiotics in food and pharmaceutical systems.

This study screened several common economic algae to optimize the extraction process of β-1,3-xylan and analyze its monosaccharide composition. The extraction process of crude xylan was optimized by alkaline extraction method, and the monosaccharide composition of crude xylan was identified by a specific enzymatic method using Caulerpa lentillifera as the main raw material. The effect of extraction time, solid-liquid ratio and NaOH concentration on the yield of crude xylan was optimized with a single factor tests followed by three-three level orthogonal experiment to study the optimal extraction conditions of crude xylan. The results showed that the extraction rate of crude xylan was influenced by the following factors: Extraction time>material-to-liquid ratio>NaOH concentration. The optimum extraction process was: Extraction time of 3 h, NaOH concentration of 2.5 mol·L−1, feed-to-liquid ratio of 1:100 g·mL−1, and the yield of crude xylan was 28.1%±0.6%. The enzymatic products were determined by thin-layer chromatography, which showed that the crude xylan extracted from Caulerpa lentillifera was β-1,3-xylan and the monosaccharide fraction was β-1,3-xylose.

Abstract Background Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation. Methods Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated. Results This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p

Soil hydraulic parameters are influenced by various inherent soil properties, such as pore structure and organic matter content, which can vary with changes in the ecosystem. However, identifying the temporal variations of soil hydraulic parameters in a co-evolving soil-vegetation system remains a challenge. This study focused on a tropical forest with significant seasonal variations in vegetation attributes, evaporation, and carbon fluxes over a five-year monitoring period. The particle batch smoother algorithm was integrated with an unsaturated flow model to identify the seasonally varied soil hydraulic parameters through assimilation of in-situ measured soil moisture. As a benchmark, the Generalized Likelihood Uncertainty Estimation method was applied to optimize soil hydraulic parameters without considering temporal variation. The results indicated that the temporally varying soil hydraulic parameters exhibited regular seasonal patterns and outperformed the unvaried soil hydraulic parameters in terms of reducing the errors in modeling of soil moisture and evaporation. Moreover, the seasonal variations in soil hydraulic parameters were closely linked to changes in the litterfall and terrestrial carbon fluxes over time. Specifically, due to the hysteresis of the transformation from litterfall to soil organic matter, the accumulated litterfall in Hot-dry season can replenish the soil organic matter, resulting in an increase in field capacity and saturated hydraulic conductivity in the Hot-rainy season. However, the intense decomposition of soil organic matter under high temperature in Hot-dry season led to a decrease in field capacity and saturated hydraulic conductivity. This study emphasizes the value of the particle batch smoother algorithm in detecting temporal variations in soil hydraulic parameters within a coevolving soil-vegetation system, thereby contributing to a more comprehensive understanding of the intricate dynamics within the ecohydrological system under a changing environment.

Ferroptosis, an iron-dependent form of programmed cell death, introduces a novel perspective on cellular demise. This study investigates the regulatory network of exosomal non-coding RNAs (ncRNAs), including miRNAs, circRNAs, and lncRNAs, in ferroptosis modulation. The primary goal is to examine the pathological roles of ferroptosis-related exosomal ncRNAs, particularly in ischemic reperfusion injuries. The research reveals intricate molecular interactions governing the regulatory interplay between exosomal ncRNAs and ferroptosis, elucidating their diverse roles in different non-malignant pathological contexts. Attention is given to their impact on diseases, including cardiac, cerebral, liver, and kidney ischemic injuries, as well as lung, wound, and neuronal injuries. Beyond theoretical exploration, the study provides insights into potential therapeutic applications, emphasizing the significance of mesenchymal stem cells (MSCs)-derived exosomes. Findings underscore the pivotal role of MSC-derived exosomal ncRNAs in modulating cellular responses related to ferroptosis regulation, introducing a cutting-edge dimension. This recognition emphasizes the importance of MSC-derived exosomes as crucial mediators with broad therapeutic implications. Insights unveil promising avenues for targeted interventions, capitalizing on the diverse roles of exosomal ncRNAs, providing a comprehensive foundation for future therapeutic strategies.

The combined effect of curcumin and docosahexaenoic acid (DHA) on liver injury has not yet been reported. We determined the synergistic effect of curcumin and DHA on the protection of WRL-68 cells from palmitic acid-induced injury, and on the inhibition of LX2 cells. A microemulsion to co-deliver both compounds was prepared by ultrasonic emulsification. Mice were fed a high-fat diet for 10 weeks to induce mild non-alcoholic fatty liver disease (NAFLD). At a dose of 5 mg/kg curcumin and 30 mg/kg DHA, the microemulsion successfully lowered serum triacylglycerol (TG) and low-density lipoprotein cholesterol levels, and significantly attenuated NAFLD. A pharmacokinetic study in rats showed that the microemulsion had a higher Cmax value for curcumin, a greater AUC0–24 value and a longer t1/2 value for both curcumin and DHA. This investigation provides a novel application of a combination of functional food ingredients to treat chronic liver disease.

Abstract Mangrove ecosystems are becoming increasingly important in global climate mitigation. However, large gaps still exist in evaluating mangroves' gross primary productivity (GPP) due to reasons such as the specific influences, for example, temperature and salt stresses are poorly described in Earth System Models (ESMs). This study developed a process‐based biogeochemical model (Mango‐GPP) to improve the GPP simulation in natural and restored mangroves. The model integrates mangrove‐specific physiological processes, including the response to salt and temperature stresses, as well as the light‐use efficiency at different growing stages. Eddy covariance flux measurements at two natural sites and one restored site in China were used to calibrate and validate Mango‐GPP. The model was calibrated by inverse analysis approach based on two cases and independently validated against the other cases. The validation results showed that it was generally capable of simulating the seasonal and interannual GPP variations at different sites. The simulated daily and annual GPPs agreed well with the observations and yielded R2 of 0.67 and 0.96, with model efficiency of 0.64 and 0.93, respectively. In comparison, Mango‐GPP showed better performances than many current satellite‐based GPP products and ESMs. The model was more sensitive to solar radiation, carbon dioxide concentration, and leaf traits. Future improvements should focus on enhancing Mango‐GPP's descriptive power of key processes, and further simulating other carbon fluxes at regional scales. This work provides a model foundation for further simulating carbon exchanges between the atmosphere, mangrove, and ocean for studying the coastal wetland restoration on regional carbon neutrality.

Abstract Background QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. Methods In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. Results Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3—not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. Conclusions QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.

Abstract Background Furmonertinib (AST2818) is a brain penetrant pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR sensitizing mutations and T790M mutation. We report the pooled central nervous system (CNS) efficacy data of furmonertinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC) from two phase 2 studies. Methods This was a pooled, post-hoc analysis of two phase 2 studies (NCT03127449 [phase 2a study of furmonertinib], NCT03452592 [phase 2b study of furmonertinib]). In the phase 2a study, patients received furmonertinib 40 mg, 80 mg, 160 mg, or 240 mg orally once daily. In the phase 2b study, all patients received furmonertinib 80 mg orally once daily. CNS efficacy of furmonertinib was analyzed in patients with baseline CNS lesions by an independent review center per Response Evaluation Criteria in Solid Tumors version 1.1. Results A total of 132 patients with baseline CNS metastases were included in this analysis. In 52 patients with measurable CNS lesions, CNS objective response rates were zero (0/1), 65% (22/34), 85% (11/13), and 25% (1/4), and CNS disease control rates were zero (0/1), 97% (33/34), 100% (13/13), and 100% (4/4) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. In patients with measurable or non-measurable CNS lesions, median CNS progression-free survival was 2.8 months (95% confidence interval [CI] 1.4–8.3), 11.6 months (95% CI 8.3–13.8), 19.3 months (95% CI 5.5-not available [NA]), and not reached (95% CI 2.8 months-NA) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. Conclusions Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutated NSCLC. Trial registration Both studies were registered on ClinicalTrial.gov. The phase 2a study was registered with NCT03127449 on April 25, 2017; The phase 2b study was registered with NCT03452592 on March 2, 2018.

Abstract Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.

Starch is the main carbohydrate source in the food system, and its hydrothermal stability during food processing is closely related to its pasting properties and nutritional functionalities. By improving the hydrothermal stability of starch, the digestion rate and degree of starch in vivo can be significantly delayed, which is of great significance for the regulation of blood glucose in vivo. From the viewpoint of the intrinsic relationships between the multi-scale structures and functionalities of starch, this review summarizes the evaluation index and evaluation method of starch hydrothermal stability and systematically discusses the key structures and processing technologies affecting starch hydrothermal stability. The pathways to modulate starch hydrothermal stability are also discussed. Additionally, perspectives regarding the current of starch hydrothermal stability modulation are proposed, which may provide theoretical foundation for the development of starch-based functional foods.

Straw return is an effective agricultural management practice for alleviating soil sickness, but only a few studies have focused on the incorporation of straw with deep plowing and rotary tillage practices in vegetable production. To determine the effects of rice straw return on Chinese cabbage clubroot, a field experiment for three consecutive years in the same area was performed. Soil microbial high-throughput sequencing, quantitative real-time polymerase chain reaction (PCR) and other methods were used to detect Chinese cabbage plant growth, clubroot occurrence, soil chemical properties and soil microbial diversity and abundance. The results showed that straw addition could significantly reduce the clubroot disease incidence. Through Illumina Miseq sequencing, the diversity of the fungi decreased obviously. The relative abundance of the phyla Proteobacteria and Firmicutes was strikingly reduced, while that of Chloroflexi was significantly increased. Redundancy analysis suggests that soil properties may also affect the soil microbial composition; changes in the microbial structure of bacteria and fungi were associated with the available phosphorus. In conclusion, the continuous addition of rice straw can promote the growth and control the occurrence of clubroot, which is closely related to the microbial composition, and the inhibition effect is proportional to the age of addition.

In this study, a novel and simple strategy is proposed based on 3D network formed by easily blending polysaccharide carrageenan (Car) and fucoidan (Fuc) without a crosslinker. The Fuc/Car dual coating effectively assists the self-assembly of soy protein-isolated (SPI)/curcumin (Cur, C) composite microcapsules (SPI/C) and achieves an excellent curcumin encapsulation efficiency (EE) up to 95.28% with a 4.16% loading capacity (LC) under optimal conditions. The resulting nanocomposites achieved a satisfying redispersibility in aqueous solution and enhanced the water solubility with a lower size dispersity index (PDI) of 0.12 and a larger zeta potential of −29.67 mV. The Fuc/Car double-layer network not only dramatically improved its thermal stability and photostability, but also provided controlled release and enhanced antioxidant activity in in vitro conditions. The underlying mechanism of the self-assembly of the curcumin-loaded nanoparticles was also addressed. The results proved the feasibility of the encapsulation of unstable hydrophobic bioactive substances (curcumin) with the dual anionic polysaccharide Fuc/Car co-stabilized SPI nanoparticles. This study paves the way for an alternative way of developing novel curcumin delivery systems and will have broad prospects in the pharmaceutical industries.

Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) are among the world’s most serious and widespread orchid viruses; they often infect orchids, causing devastating losses to the orchid industry. Therefore, it is critical to establish a method that can rapidly and accurately detect viruses in the field using simple instruments, which will largely reduce the further spread of viruses and improve the quality of the orchid industry and is suitable for mass promotion and application at grassroots agrotechnical service points. In this investigation, we established a rapid amplification method for virus detection at 39 °C for 35 min to detect the presence of CymMV and ORSV simultaneously, sensitively, and specifically in orchids. Primers for the capsid protein (CP)-encoding genes of both viruses were designed and screened, and the reaction conditions were optimized. The experimental amplification process was completed in just 35 min at 39 °C. There were no instances of nonspecific amplification observed when nine other viruses were present. The RPA approach had detection limits of 104 and 103 copies for pMD19T-CymMV and pMD19T-ORSV, respectively. Moreover, the duplex RT-RPA investigation confirmed sensitivity and accuracy via a comparison of detection results from 20 field samples with those of a gene chip. This study presents a precise and reliable detection method for CymMV and ORSV using RT-RPA. The results demonstrate the potential of this method for rapid virus detection. It is evident that this method could have practical applications in virus detection processes.

To improve the survivability of probiotics, Lactobacillus plantarum was microencapsulated using pufferfish skin gelatin (PSG)-based wall materials by spray-drying. This work investigated the protective effect of three different pH-dependent proteins (sodium caseinate (SC), soy protein isolate (SPI), and whey protein isolate (WPI)) combined with PSG on L. plantarum. The experimental results of spray-drying with an inlet temperature of 120 °C and an outlet temperature of 80 °C, storage at 4 °C for 6 months, simulated digestion, and turbidity indicated that PSG/SC had better stability and encapsulation effects and was more suitable to encapsulate L. plantarum than PSG/SPI and PSG/WPI. The optimum preparation conditions for L. plantarum microcapsules were a PSG/SC mass ratio of 2:1, an SC concentration of 20 g/L, and a cell concentration of 10 g/L. The encapsulation efficiency of the obtained microcapsules was 95.0%, and the survival rate was 94.2% in simulated gastric fluid for 2 h and 98.0% in simulated intestinal fluid for 2 h. Amino acid composition analysis exhibited that the imino acid and aspartic acid contents of PSG were 27.98 and 26.16 g/100 g protein, respectively, which was much higher than commercial bovine gelatin. This characteristic was favorable to the high encapsulation efficiency and stability of microcapsules. In vitro release experiments showed that the PSG/SC microcapsules did not disintegrate in simulated gastric fluid for 2 h but could completely release in simulated intestinal fluid for 2 h, which can maintain the high survivability of L. plantarum in simulated digestion. In general, this study demonstrated that microcapsules using PSG/SC as wall materials can effectively improve the survivability of probiotics and have great potential for application in probiotic products.

Abstract A novel stripline diplexer design using frequency‐dependent couplings (FDC) to achieve multiple transmission zeros is developed in this paper. The transmission zeros generated by FDCs are flexible and controllable; on the basis of the existing cross‐coupled, more transmission zeros are introduced to improve the frequency selection characteristics. Based on this characteristic, the authors synthesized and designed a 2.6‐GHz diplexer, its transmitting channel filter is five orders with three transmission zeros, and the receiving channel filter is four orders with three transmission zeros. The authors fabricated and measured it, in narrowband, the tested results, synthesis responses and simulation results are well matched with each other, which will provide more flexibility in the design of diplexers for wireless communication system.

The North Huicheng Basin strike-slip fault system is on the northeastern frontier of the Tibetan Plateau and separates the West and East Qinling differential orogeny. However, the deformation mechanism of this strike-slip fault system and its exact tectonic significance are unclear. Here, we carried out systematic field structural analysis, physical analog modeling, and multiproxy geochronological dating to address these issues. The field structural analysis indicates that the North Huicheng Basin strike-slip fault system was induced from the plate-like movement of the West and East Qinling Orogens, which underwent multiple left-lateral strike-slip faulting and controlled salient and recessed structures. The scaled physical analog experiment results confirm this hypothesis and reveal the primary spatial-temporal deformational kinematic process. Combined with published works, multiproxy geochronological dating (zircon U‒Pb age of 213 Ma, biotite 40Ar/39Ar age of 203 Ma, and apatite fission-track age of 56 Ma) outlines the main thermal history of the hanging wall. Based on the above facts, the integrated research suggests that multistage strike-slip faulting played a significant role in the main tectonic events, that is, late Triassic magmatic emplacement, Jurassic/Cretaceous local pull-apart, and Cenozoic rapid exhumation driven by Tibetan Plateau growth.

Although phenology and growth traits of leaves or woods have been the focus of research on growth-climate relationships, more is needed regarding whether there is a consistent growth response of different organs to environmental change. However, such work is crucial to accurately assess the impact of climate change on tree growth. Here, the growth timing, duration, rate, and increment of Picea meyeri needles, shoots, and stems were examined, and the corresponding environmental effects were revealed along an altitudinal gradient (2040–2740 m a.s.l.) in North-Central China during 2016 and 2017. The three organs showed a consistent altitudinal variation in growth onset timing, but a different variation in other traits; the growth duration, rate, and increment of needles changed slightly while those of shoots and stems dropped markedly with altitude. The air temperature was the key environmental factor driving the altitudinal variation. For each 1 °C increase in air temperature, the onset timing of needle and shoot elongation and xylem cell production was synchronously advanced by 3.3–3.7 ± 0.2 days; the peak timing was advanced by 3.4 ± 0.2 days, 2.2 ± 0.1 days, and 0 days; and the cessation timing was delayed by −3.8 ± 0.0 days, 2.1 ± 0.3 days, and 2.4 ± 0.1 days. Meanwhile, the duration was lengthened by 0 days, 5.6 ± 0.3 days, and 6.4 ± 0.2 days, respectively; the average rate was improved by 0%, 7.0 ± 1.2%, and 6.5 ± 0.5%, respectively; the increment was increased by 1.3 ± 0.1%, 8.2 ± 0.4%, and 11.0 ± 0.4%, respectively. These findings suggested that the aboveground vegetative growth of P. meyeri exhibits different temperature sensitivities; stem growth will benefit more from future warming than shoot and needle growth. It adds a new clue to conducting growth-climate relationship studies, and the response difference of organ growth to temperature should be considered in revealing future climate warming on tree growth.

Abstract Background Iruplinalkib (WX-0593) is an anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor. Here we reported the single-arm, phase II study (INTELLECT) results of the efficacy and safety of iruplinalkib for ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC) patients. Methods ALK-positive crizotinib-resistant advanced NSCLC patients aged ≥18 years, with Eastern Cooperative Oncology Group performance status of 0–2 were eligible. Patients received iruplinalkib 180 mg orally once daily for a 21-day cycle with a 7-day lead-in phase at 60 mg orally once daily. The primary endpoint was the independent review committee (IRC)-assessed objective response rate (ORR). Results From August 7, 2019, to October 30, 2020, 146 patients were included. As of the data cut-off date on November 30, 2021, the median follow-up time was 18.2 months (95% confidence interval [CI] 16.8–18.8). IRC-assessed ORR and disease control rate (DCR) were 69.9% (95% CI 61.7–77.2%) and 96.6% (95% CI 92.2–98.9%), respectively. Investigator-assessed ORR and DCR were 63.0% (95% CI 54.6–70.8%) and 94.5% (95% CI 89.5–97.6%), respectively. Investigator-assessed median duration of response and progression-free survival (the same as median time to progression) were 13.2 months (95% CI 10.4–17.7) and 14.5 months (95% CI 11.7–20.0), respectively. Corresponding IRC-assessed results were 14.4 months (95% CI 13.1–not evaluable [NE]), 19.8 months (95% CI 14.5–NE), and NE (95% CI 14.5–NE), respectively. Investigator-assessed intracranial ORRs were 46% (41/90, 95% CI 35–56%) in patients with central nervous system metastases and 64% (27/42, 95% CI 48–78%) in patients with measurable intracranial lesions. Overall survival data were immature. Treatment-related adverse events (TRAEs) occurred in 136/146 (93.2%) patients. The most common TRAEs were aspartate aminotransferase increased (63 [43.2%]), alanine aminotransferase increased (54 [37.0%]), and blood creatine phosphokinase increased (51 [34.9%]). Dose interruption, reduction, and discontinuation due to TRAEs occurred in 21 (14.4%), 16 (11.0%), and four (2.7%) patients, respectively. Conclusions In this study, iruplinalkib (WX-0593) demonstrated favorable efficacy and manageable safety profiles in patients with ALK-positive crizotinib-resistant advanced NSCLC. Iruplinalkib could be a new treatment option for this patient population. Trial registration Center for Drug Evaluation of National Medical Products Administration of China: CTR20190789, registered on April 28, 2019; ClinicalTrials.gov: NCT04641754, registered on November 24, 2020.

In order to study the separation and purification process and antioxidant activity of Sargassum horneri polyph-enols, on the basis of ultrasonic assisted extraction of Sargassum horneri polyphenols, macroporous adsorption resin column chromatography was used to separate and purify Sargassum horneri polyphenol extract, and VC was used as the control to analyze its antioxidant activity in vitro. The results showed that the macroporous adsorption resin LX-158 exhibited the best adsorption and analysis conditions. The equilibrium time for static adsorption and analysis was 5 h. The following circumstances were ideal for dynamic adsorption and analysis: The flow rate of crude extract and eluent was 3 mL/min, the loading volume was 10 mL, the eluent was a 40% ethanol solution, and the eluent volume was 120 mL. The purity of Sargassum horneri polyphenols increased from 7.52% to 40.31% under these conditions. Antioxidant activity studies revealed that varied doses of Sargassum horneri polyphenols had noticeable scavenging effects on DPPH radical, ABTS radical, superoxide anion radical, hydroxyl radical and Fe3+ reducing power. With the increase of polyphenol concen-tration, its antioxidant capacity improved, and the IC50 was 6.60 μg/mL, 75.70 μg/mL, 2.22 mg/mL, 5.62 mg/mL, respec-tively. The purification process is feasible and stable, and it can be used as a process condition for the purification of polyphenols from Sargassum horneri.

Abstract Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non–small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2‐altered NSCLC, including conventional chemotherapy, programmed death 1 (PD‐1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody‐drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T‐DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2‐mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2‐targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2‐altered NSCLC, focusing on the diagnosis and treatment strategies.

Abstract Background The aim of this study is to investigate the prevalence of myopia and high myopia and the associated risk factors in key schools in Xi'an, China. Methods This cross-sectional study started in September 2021 and was conducted for one month. A total of 11,011 students from 10 key primary schools, five key junior high schools and five key high schools in Xi'an were randomly selected to undergo visual acuity measurement and non-cycloplegic autorefraction. The questionnaire was completed by the students and their parents together. Results The prevalence of myopia and high myopia in key schools were 75.7% and 9.7%, respectively. The prevalence of myopia and high myopia rose significantly as grade or age increased (all P < 0.001), and the prevalence of myopia and high myopia in females was higher than that in males (P < 0.001, P < 0.5). According to the multivariable logistic regression analysis, older age (OR=1.42), female compared with male (OR=1.43), having one myopic parent (OR=1.64), having two myopic parent (OR=2.30) and often taking extracurricular tuition (OR=1.35) were more likely to be associated with develop myopia (P < 0.001). Older age (OR=1.39), having one myopic parent (OR=2.29), having two myopic parent (OR= 3.69), and often taking extracurricular tuition (OR=1.48) were more likely to be associated with high myopia (P < 0.001). Conclusions The overall rate of myopia and high myopia in key schools in Xi'an, China, is extremely high. Myopia and high myopia are associated with increasing age, parents’ myopia, few outdoor exercises, and extracurricular tuition. Myopia is also associated with female and not having the habit of "one punch, one foot, one inch (when reading and writing, 10 cm from the chest to the table, 33 cm from the eye to the book and 3.3 cm from the tip of the pen to the finger)".