A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor. METHODS: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC). FINDINGS: Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n = 18), B (n = 17), and C (n = 18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2 months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE. CONCLUSIONS: Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety. FUNDING: Shanghai Henlius Biotech, Inc.

Rice-crayfish farming system promote subsoil microbial residual carbon accumulation and stabilization by mediating microbial metabolism process.

Rice-crayfish farming systems (RCs) can help mitigate climate change by enhancing soil organic carbon (SOC) sequestration. However, the mechanisms that govern the responses of microbial residues carbon (MRC), a key component of SOC, in RCs are not fully understood. We conducted a 6-year field experiment comparing RCs and rice monoculture systems (RMs). Specifically, we explored how MRC formation and stabilization differ between the two systems and how those differences are linked to changes in the metabolic processes of microbes. Results showed that MRC levels in RCs were 5.2 % and 40.0 % higher in the topsoil and subsoil, respectively, compared to RMs, indicating depth-dependent effects. Notably, MRC accumulation and stabilization in RCs were promoted through a cascade of processes of dissolved organic carbon (DOC) accessibility-microbial metabolism-mineral protection. In addition, the mechanism of MRC accumulation in subsoil differed between the two systems. Specifically, RMs improved accessibility of DOC by reducing humification and aromaticity of subsoil DOC, which helped microbes access to resources at lower cost. This decreased the respiration rate of microbes, thereby increasing microbial carbon pump (MCP) efficiency and thus promoting MRC accumulation. By contrast, the crayfish in RCs facilitated carbon exchange between topsoil and subsoil through their burrowing behaviors. This increased carbon allocation for microbial metabolism in the subsoil, supporting a larger microbial population and thus enhancing the MCP capacity, while reducing MRC re-decomposition via enhanced mineral protection, further increasing subsoil MRC accumulation. That is, MRC accumulation in the subsoil of RCs was predominantly driven by microbial population numbers (MCP capacity) whereas that of RMs was mostly driven by microbial anabolic efficacy (MCP efficiency). Our findings reveal a key mechanism by which RCs promoted soil MRC accumulation and stabilization, highlighting the potential role of DOC accessibility-microbial metabolism-mineral protection pathway in regulating MRC accumulation and stabilization.

Adsorption Potential, Speciation Transformation, and Risk Assessment of Hg-, Cd-, and Pb-Contaminated Soils Using Biochar in Combination with Potassium Dihydrogen Phosphate.

The objective of this study is to develop a remediation technology for composited heavy metal-contaminated soil. Biochars (BC300, BC400, and BC500) derived from corn were combined with potassium dihydrogen phosphate (KH2PO4) to immobilize and remove heavy metal ions, including mercury (Hg2+), cadmium (Cd2+), and lead (Pb2+). The adsorption kinetics of metal ions in aqueous solutions with different concentrations was tested, and the fitting effects of the two models were compared. The findings demonstrate that the joint application of biochar and KH2PO4 could markedly enhance the immobilization efficacy of Pb2+, whereas the utilization of KH2PO4 on its own exhibited a more pronounced immobilization impact on Cd2+. Furthermore, the present study underscores the shortcomings of various remediation techniques that must be taken into account when addressing heavy metal-contaminated soils. It also emphasizes the value of comprehensive remediation techniques that integrate multiple remediation agents. This study offers a novel approach and methodology for addressing the intricate and evolving challenges posed by heavy metal contamination in soil. Its practical value and potential for application are significant.

Potassium deficiency enhances imbalances in rice water relations under water deficit by decreasing leaf hydraulic conductance.

Potassium (K+) is an essential macronutrient for appropriate plant development and physiology. However, little is known about the mechanisms involved in the regulation of leaf water relations by K under water deficit. A pot experiment with two K supplies of 0.45 and 0 g K2O per pot (3 kg soil per pot) and two watering conditions (well-watered and water-deficit) was conducted to explore the effects of K deficiency on canopy transpiration characteristics, leaf water status, photosynthesis, and hydraulic traits in two rice genotypes with contrasting resistance to drought. The results showed that K deficiency reduced canopy transpiration rate by decreasing stomatal conductance, which led to higher canopy temperatures, resulting in limited water deficit tolerance in rice. In addition, K deficiency led to further substantial reductions in leaf relative water content and water potential under water deficit, which increased the imbalance in leaf water relations under water deficit. Notably, K deficiency limited leaf gas exchange by reducing leaf hydraulic conductance, but decreased the intrinsic water use efficiency under water deficit, especially for the drought-resistant cultivar. Further analysis of the underlying process of leaf hydraulic resistance revealed that the key limiting factor of leaf hydraulic conductance under K deficiency was the outside-xylem hydraulic conductance rather than the xylem hydraulic conductance. Overall, our results provide a comprehensive perspective for assessing leaf water relations under K deficiency, water deficit, and their combined stresses, which will be useful for optimal rice fertilization strategies.

Butane Tetracarboxylic Acid Grafted on Polymeric Nanofibrous Aerogels for Highly Efficient Protein Absorption and Separation.

Developing high-performance and low-cost protein purification materials is of great importance to meet the demands for highly purified proteins in biotechnological industries. Herein, a facile strategy was developed to design and construct high-efficiency protein absorption and separation media by combining aerogels' molding techniques and impregnation processes. Poly (ethylene-co-vinyl alcohol) (EVOH) nanofibrous aerogels (NFAs) were modified by grafting butane tetracarboxylic acid (BTCA) over them in situ. This modification was carried out using polyphosphoric acid as a catalyst. The resulting EVOH/BTCA NFAs exhibited favorable comprehensive properties. Benefiting from the highly interconnected porous structure, good underwater compressive properties, and abundant absorption ligands, the obtained EVOH/BTCA NFAs possessed a high static absorption capacity of 1082.13 mg/g to lysozyme and a short absorption equilibrium time of about 6 h. A high saturated dynamic absorption capacity for lysozyme (716.85 mg/g) was also realized solely by gravity. Furthermore, EVOH/BTCA NFAs displayed excellent reusability, good acid and alkaline resistance, and unique absorption selectivity performance. The successful synthesis of such aerogels can provide a potential candidate for next-generation protein absorbents for bio-separation and purification engineering.

Self-Assembly Study of Block Copolypeptoids in Response to pH and Temperature Stimulation.

Polypeptoids with well-designed structures have the ability to self-assemble into nanomaterials, which have wide potential applications. In this study, a series of diblock copolypeptoids were synthesized via ring-opening polymerization followed by click chemistry and exhibited both temperature and pH stimulation responsiveness. Under specific temperature and pH conditions, the responsive blocks in the copolypeptoids became hydrophobic and aggregated to form micelles. The self-assembly process was monitored using the UV-Vis and DLS methods, which suggested the reversible transition of free molecules to micelles and bigger aggregates upon instituting temperature and pH changes. By altering the length and proportion of each block, the copolypeptoids displayed varying self-assembly characteristics, and the transition temperature could be tuned. With good biocompatibility, stability, and no cytotoxicity, the polypeptoids reported in this study are expected to be applied as bionanomaterials in fields including drug delivery, tissue engineering, and intelligent biosensing.

Preparation of Peptoid Antifreeze Agents and Their Structure-Property Relationship.

The development of nontoxic and efficient antifreeze agents for organ cryopreservation is crucial. However, the research remains highly challenging. In this study, we designed and synthesized a series of peptoid oligomers using the solid-phase submonomer synthesis method by mimicking the amphiphilic structures of antifreeze proteins (AFPs). The obtained peptoid oligomers showed excellent antifreeze properties, reducing the ice crystal growth rate and inhibiting ice recrystallization. The effects of the hydrophobicity and sequence of the peptoid side chains were also studied to reveal the structure-property relationship. The prepared peptoid oligomers were detected as non-cytotoxic and considered to be useful in the biological field. We hope that the peptoid oligomers presented in this study can provide effective strategies for the design of biological cryoprotectants for organ preservation in the future.

Reaction Process of Solid Waste Composite-Based Cementitious Materials for Immobilizing and Characterizing Heavy Metals in Lead and Zinc Tailings: Based on XRD, SEM-EDS and Compressive Strength Characterization.

This study investigates the synergistic effect and mechanism of gelling materials with blast furnace slag (BFS), steel slag (SS) and desulphurization gypsum (DG) as the main components on the hardening of heavy metal ions by lead and zinc tailings. It is found that lead and zinc tailing (LZT) is mainly composed of dolomite and quartz and contain small amounts of calcium, aluminum, iron, magnesium and other elements as well as heavy metals such as lead and zinc. By the mechanical activation method, it is found that the lead and zinc tailings powder has the largest specific surface area and the highest activity index when the ball milling time is 2 h. At a hardening timepoint of 28 d, the calcite crystals in the samples are intertwined with the amorphous C-S-H gel (C-S-H gels are mainly composed of 3CaO∙SiO2 and 2CaO∙SiO2), which enhances the structural strength of the samples. The chemical reaction analysis confirmed that the formation of calcite is a major driver for the hydration reaction of the steel slag-desulphurization gypsum (SSSDG) system. Overall, the slag, steel slag and desulphurization gypsum solid waste-based gelling materials have synergistic effects in hardening heavy metals by limiting the leaching of metal ions, adsorbing metal ions and hardening heavy metals, and facilitating the hydration process through the formation of compound salt precipitates.

Rectify representation bias in vision-language models for long-tailed recognition.

Natural data typically exhibits a long-tailed distribution, presenting great challenges for recognition tasks. Due to the extreme scarcity of training instances, tail classes often show inferior performance. In this paper, we investigate the problem within the trendy visual-language (VL) framework and find that the performance bottleneck mainly arises from the recognition confusion between tail classes and their highly correlated head classes. Building upon this observation, unlike previous research primarily emphasizing class frequency in addressing long-tailed issues, we take a novel perspective by incorporating a crucial additional factor namely class correlation. Specifically, we model the representation learning procedure for each sample as two parts, i.e., a special part that learns the unique properties of its own class and a common part that learns shared characteristics among classes. By analysis, we discover that the learning process of common representation is easily biased toward head classes. Because of the bias, the network may lean towards the biased common representation as classification criteria, rather than prioritizing the crucial information encapsulated within the specific representation, ultimately leading to recognition confusion. To solve the problem, based on the VL framework, we introduce the rectification contrastive term (ReCT) to rectify the representation bias, according to semantic hints and training status. Extensive experiments on three widely-used long-tailed datasets demonstrate the effectiveness of ReCT. On iNaturalist2018, it achieves an overall accuracy of 75.4%, surpassing the baseline by 3.6 points in a ResNet-50 visual backbone.

Influence of Mineral Composition on Rock Mechanics Properties and Brittleness Evaluation of Surrounding Rocks in Soft Coal Seams.

The structural fracture of the coal seam with its low permeability is the dominant reason for the "difficult gas out" of the broken soft coal seam. The brittleness of the roof and floor rock stratum of the broken soft coal seam has a significant effect on the fracture extension pressure of the surrounding rock after casing perforation and hydraulic fracturing of the horizontal well for coalbed methane (CBM). In this paper, 15 rock samples were scientifically collected from the roof and floor of the main mining coal seam of the Early Permian coal-bearing series in the Xinxie-1 well of the Huainan Coalfield in Anhui Province, China. On the basis of mineral composition analysis of these samples, the influence of mineral composition on the mechanics properties of the rock at the roof and floor of the coal seam was investigated. The correlation analysis and gray correlation analysis were adopted to construct an evaluation method for the brittleness of the rock at the roof and floor of the coal seam based on the mineral content. The results indicated that the most significant compositions of the minerals in the rock at the roof and floor of the broken soft coal seam were quartz and clay minerals. The most significant types of rock cementation are quartz agglomeration and rhodochrosite cementation. Pore destruction as a result of cementation was much greater than that of compaction. In comparison to clay minerals, the variation in the content of brittle minerals such as quartz, plagioclase, and siderite in the rock showed more sensitivity to the mechanics properties of the rock. The more sensitive minerals for compressive strength (CS), shear strength (SS), modulus of elasticity (E), softening coefficient (K), and Poisson's ratio (µ) are quartz, those for tensile strength (TS) are plagioclase and siderite, and those for Poisson's ratio are clay minerals. Based on the established mineral content weighting analysis method, it was calculated that the brittleness index (BI) of the rocks at the roof of the 13-1, 11-2, 9-2, and 4-2 coal seams was larger, which was advantageous for the formation of longer fracturing crack networks. This is theoretical guidance for the optimization of horizontal well fracturing design in the deep coal beds of the Huainan Coalfield.

Enhancing Electrochemical Performance of Aluminum-Oxygen Batteries with Graphene Aerogel Cathode.

Aluminum-oxygen batteries (AOBs) own the benefits of high energy density (8.14 kWh kg-1), low cost, and high safety. However, the design of a cathode with high surface area, structure integrity, and good catalytic performance is still challenging for rechargeable AOBs. Herein, the fabrication of a robust self-supporting cathode using 3D graphene aerogel (3DGA) for rechargeable AOBs is demonstrated. Electroanalysis showed that the 3DGA presented good catalytic activity in both oxygen reduction and evolution reactions, which allowed the AOB to operate for >90 cycles with low overpotentials at a current density of 0.2 mA cm-2, and a high Coulombic efficiency of ca. 99% using ionic liquid as electrolyte. In comparison, the cell with the carbon paper cathode can only cycle for 50 rounds. The excellent cyclic performance can be attributed to the porous structure, large surface area, good electric conductivity, and catalytic activity of the 3DGA, which is prospective to be applied for other metal-air batteries, fuel cells, and supercapacitors.

The Developmental Toxicity and Endocrine-Disrupting Effects of Fenpropathrin on Gobiocypris rarus during the Early Life Stage.

In the present study, the developmental toxicity and endocrine-disrupting effects of fenpropathrin on Gobiocypris rarus during the early life stage were studied using a semi-static water exposure method. The results showed that the LOEC (lowest observed effect concentration) of fenpropathrin on the incubation of rare minnow embryos was above 2.5 µg·L-1. The LOEC and NOEC (no observed effect concentration) of fenpropathrin on the developmental malformations and death indicators were 2.0 and 1.5 µg·L-1, respectively. After exposure to 1.5 µg·L-1 of fenpropathrin for 31 days, the expressions of androgen receptor genes (AR) and sex hormone-synthesis-related genes (CYP17 and CYP19a) were significantly decreased and the expressions of thyroid hormone receptor genes (TRß) and aryl hydrocarbon receptor genes (AhR1a and AhR2) were significantly increased in juvenile Gobiocypris rarus. The expression levels of the androgen receptor gene (AR), estrogen receptor gene (ER1), and the sex hormone-synthesis-related genes (HMGR, CYP17, and CYP19a) were significantly decreased, while the estrogen receptor gene (ER2a), thyroid hormone receptor gene (TRß), and aromatic hydrocarbon receptor genes (AhR1a and AhR2) were upregulated in juvenile Gobiocypris rarus under exposure to 2.0 µg·L-1 of fenpropathrin. Relatively low concentrations of fenpropathrin can affect the expression of sex hormone receptor genes, genes related to sex hormone synthesis, thyroid hormone receptor genes, and aromatic hydrocarbon receptor genes, thus interfering with the reproductive system, thyroid system, and metabolic level in Gobiocypris rarus. Therefore, more attention should be paid to the endocrine-disrupting effect caused by the pyrethroid insecticides in the water environment. Furthermore, studies on the internal mechanism of the endocrine-disrupting effect of pyrethroid insecticides on fish is needed in the future.