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The study of loaded meshing characteristics and dynamic behavior is significant for evaluating the stability of hypoid gear under actual working conditions. Loaded tooth contact analysis (LTCA) of a hypoid gear drive under different loads is carried out. The equivalent meshing force, loaded transmission error (LTE), comprehensive elastic deformation, and time-varying meshing stiffness (TVMS) are investigated. Results show that the LTE and TVMS are sensitive to load, and the LTE and TVMS curves show obvious asymmetric as the load increases. Under low load conditions, the actual contact ratio increases significantly with the increase of load, but tends to be flat when the load reaches a certain range. The obtained TVMS and LTE are fitted by higher Fourier series and introduced into an 8-DOF dynamic model. By comparing the time history diagram, phase diagram, Poincaré section, and spectrum, the dynamic characteristics of the system under different loads are contrasted. On low load condition, the system may exhibit chaotic motion in certain meshing frequency bands and damping ratio intervals. While the tooth backlash increases to a critical value, the system may change to chaotic motion from periodic motion. The results provided a basis for improving the meshing performance of hypoid gear.

The earliest occurrence of chlorosis at the tips of the oldest leaves is widely recognized as a reliable indicator for diagnosing potassium (K) deficiency and determining the need for K fertilizer. However, hidden K deficiency, typically associated with a decrease in individual leaf photosynthetic area, precedes the onset of visible yellowing symptoms. These concealed symptoms pose challenges for the early diagnosis of K deprivation in plants. The two distinct stages of deficiency exhibit different photosynthetic performances, which are speculated to be closely linked to the subcellular K+ distribution. This minireview focuses on investigating K+ dynamics across subcellular compartments, along with the involvement of functional transporter proteins and ion channels during K deficiency. We propose potential mechanisms by which subcellular K+ regulates photosynthetic capacity under both hidden and visual K deficiency conditions, which sheds new light on the diagnosis of K deficiency. Additionally, future research prospects and areas deserving further investigation are also outlined.

In this study, we explore the dynamic nature of metallocene catalysts during ethylene/isoprene E/IP) copolymerization, with a focus on the influence of various reaction parameters. Challenges, why do olefinic catalysts show lower activity and molecular weight (Mw) at higher temperatures and low activity with higher diene content? Firstly, we investigate the observed phenomena of decreased catalyst activity and Mw at elevated temperatures using 1.25 μmole of the metallocene. Notably, a substantial increase in active sites from 30 °C to 40 °C, reaching a peak of 89 %. Surprisingly, further temperature increments lead to a noticeable decline in active sites. At 30 °C, the active site primarily engages in the insertion of IP through 3,4 connections, with no detectable cis-1,4 or trans-1,4 connections, which suggests a lack of stereoselectivity at this temperature. At 40–50°C, cis/trans-1,4 connections and active sites are approaching a higher level. This implies a reduction in chain transfer reactions, making catalytic active sites more favorable to cis/trans-1,4 connections. Secondly, we observe a remarkable impact of IP concentration in the E/IP copolymers, active centers, and activity show stability when the amount of IP was 0.116–0.48 mol/L and then started to decline when the amount of IP 0.96 mol/L, indicating a threshold beyond which deactivation occurs. Increasing IP concentration not only reduces activity and active sites but also fails to reactivate dormant polyethylene sites. The Mw and active centers of copolymers progressively decrease with elevated IP concentration, suggesting a faster chain transfer reaction with IP compared to E.

Mine sudden water is one of the most threatening geological hazards during mining production, so rapid and effective identification of sudden water sources is the key to prevent mine water damage. In this study, we analyzed the water chemistry of Panji Coal Mine aquifer and carried out the testing and analysis of strontium isotopes of water in the adjacent water rock, selected seven discriminatory indexes: 87Sr/86Sr, Ca2+, Na++K+, Mg2+, HCO3−, SO42−, Cl−, combined with principal component analysis and Fisher’s theory, principal component analysis and distance discriminatory theory, principal component analysis and BP Neural network, to establish the discriminatory models of mixed water sources based on strontium isotopes (Sr-F model, Sr-D model, Sr-B model), and use the models to discriminate unknown water samples. The results show that the Sr-B model based on strontium isotopes has the best discriminative effect, and its accuracy reaches 95%. Therefore, the identification model of water inrush sources based on principal component analysis and BP neural network can effectively improve the identification accuracy of water inrush sources, accurately identify water inrush sources in adjacent limestone aquifers, and provide guarantee for mine safety production.

Cutterhead torque is a key operational parameter for earth pressure balance (EPB) TBM tunneling in soil strata. The effective management of cutterhead torque can significantly maintain face stability and ensure the tunneling machine operates steadily. The Shenzhen Metro Line 12 project at Shasan Station utilized the world’s largest rectangular pipe jacking machine for constructing the subway station. This project has enabled the collection of relevant data to analyze the factors influencing cutterhead torque and to establish a predictive model. The data encompass an abundant array of cutterhead design parameters, operational parameters, properties of the excavated soil, and environmental factors, revealing the distribution characteristics of cutterhead torque during tunneling. The correlation between various factors and cutterhead torque has been examined. By employing multiple regression analysis and a Levenberg–Marquardt (L-M) algorithm-based neural network, an optimal prediction model for EPB cutterhead torque has been developed. This prediction model incorporates various factors, including cutterhead diameter, RPM, soil chamber pressure, soil shear strength, and the soil consistency index. And the degree of influence of each factor on the cutter torque was also revealed. The prediction results demonstrated good accuracy compared to previous models, providing valuable insights and guidance for EPB TBMs or pipe jacking machines operating in soil strata. The current limitations of this model and suggestions for future work have also been addressed.

Abstract We retrospectively enrolled 325 gastric cancer (GC) patients to investigate the associations of programmed death ligand‐1 (PD‐L1) expression with clinicopathological characteristics by different scoring methods and different cutoff values. PD‐L1 expression was evaluated by the tumor proportion score (TPS) and the combined positive score (CPS). The positive rate of PD‐L1 TPS ≥1%, CPS ≥1, CPS ≥5 and CPS ≥10 in our study were 12.0%, 87.4%, 69.8% and 42.2%, respectively. Multivariate analysis showed that PD‐L1 CPS ≥5 was related to high expression of Ki67 (OR = 2.658, 95% CI: 1.401–5.045, p = .003) and pTNM staging (p = .033). PD‐L1 CPS ≥10 was correlated with larger tumor size (OR = 2.322, 95% CI: 1.052–5.127, p = .037) and lymph node metastasis (OR = 2.495, 95% CI: 1.293–4.814, p = .006). It is expected that these results can provide a reference for screening GC patients with high PD‐L1 expression level.

Pigeon paramyxovirus type 1 (PPMV-1), an antigenic variant of avian paramyxovirus type 1 (APMV-1), mainly infects pigeons. PPMV-1 genotype VI is the dominant genotype infecting pigeons in China. Human infection of avian paramyxovirus was rarely reported, and usually developed mild symptoms, such as conjunctivitis. We detected PPMV-1 in the lower respiratory sample from a fatal case with severe pneumonia; this patient aged 64 years presented cough, fever, and haemoptysis for 8 days and was admitted to hospital on Dec 26, 2020. He developed acute respiratory distress syndrome and sepsis in the following days and died of multiple organ failure on Jan 7, 2021. Sputum and blood culture reported multidrug-resistant Acinetobacter baumannii (ABA) for samples collected on days 22 and 19 post-illness, respectively. However, clinical metagenomic sequencing further reported PPMV-1 besides ABA in the bronchoalveolar lavage fluid. The PPMV-1 genome showed 99.21% identity with a Chinese strain and belonged to VI genotype by BLAST analysis. Multiple basic amino acids were observed at the cleavage site of F protein (113RKKRF117), which indicated high virulence of this PPMV-1 strain to poultry. The patient had close contact with pigeons before his illness, and PPMV-1 nucleic acid was detected from the pigeon feather. PPMV antibody was also detected in the patient serum 20 days after illness. In conclusion, concurrent PPMV-1 genotype VI.2.1.1.2.2 and ABA infection were identified in a fatal pneumonia case, and cross-species transmission of PPMV-1 may occur between infected pigeons and the human being.

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.

Abstract The aim was to analyze the clinical characteristics of adverse drug reactions (ADRs) induced by Osimertinib and their effects on the prognosis, so as to further provide reference for clinical medication. This was a retrospective study, and 66 nonsmall cell lung cancer (NSCLC) patients who had ADR in the 2nd‐line treatment with Osimertinib from January 2017 to December 2018 were included. Clinical characteristics and survival in subgroups of Osimertinib‐related ADRs were analyzed. The majority of patients who developed ADRs after the 2nd‐line treatment of Osimertinib were mainly middle‐aged and elderly women. Osimertinib‐related ADRs were mainly found in the skin, respiratory and digestive systems. The most common ADRs were rash (69.70%), diarrhea (66.67%), stomatitis (54.55%), and fatigue (51.52%). The degree of Osimertinib‐related ADRs was tolerable. Only seven patients experienced grade 3 ADRs, all of which involved the skin system. Exactly 92.42% of patients had more than two adverse reactions. The median PFS was influenced by the type, quantity, and severity of Osimertinib‐related ADRs. Osimertinib‐related ADRs are closely related to the prognosis of patients so that more attention should be paid to monitoring the occurrence of ADRs in clinical use of Osimertinib, especially ADRs in the skin, respiratory system and digestive system.

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.

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 (TRβ) 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 (TRβ), 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.

Chlorosis at leaf margins is a typical symptom of potassium (K) deficiency, but inappropriate application of K with other nutrients often masks symptoms of K deficiency. A two-year field experiment was conducted to measure the interactive effects of N and K on leaf photosynthesis and dry matter accumulation and the resulting growth dilution effect on K concentration and leaf K deficiency symptoms. N application aggravated the imbalance of N and K nutrients and further exacerbated K deficiency symptoms under K limitation. Synergistic effects of N and K promoted plant growth, amplified the growth dilution effect, and reduced the critical K concentration in leaves. Using 90% of the maximum shoot biomass as a threshold, the critical K concentration was 0.72% at the recommended N (N180) fertilization level. The critical K concentration increased by 62.5% owing to the reduced biomass under insufficient N (N90) supply. In contrast, high N (N270) reduced the critical K concentration (0.64%), accelerating chlorophyll decomposition and exacerbating K deficiency symptoms. The basis of changing the critical K concentration by magnifying growth dilution effect was the functional synergistic effect of N and K on photosynthetic characteristics. Under insufficient N, the low maximum carboxylation rate (Vcmax) limited the net photosynthetic rate (An) and necessitated more K to maintain high CO2 transmission capacity, to improve the total conductance gtot /Vcmax ratio. High N supply increased gtot and Vcmax, possibly mitigating the effect of K reduction on photosynthesis. In conclusion, it is unwise to judge K status of plants only by K concentration without accounting for crop mass (or dilution effect), critical K concentration and deficiency symptoms are affected by N fertilization, and the synergistic effect of N and K on leaf photosynthesis is the foundation of maximal growth of plants under diverse critical K concentrations.

Abstract Background The prognosis difference based on the depth of tumor muscularis propria invasion in gastric cancer (GC) was still debated, and therapy strategy for stage IB GC patient required further investigation. Methods A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in superficial muscularis propria (sMP) group and 195 in deep muscularis propria (dMP) group. Results The overall survival (OS) was significantly better for patients in sMP group than for patients in dMP group (P = 0.007). In multivariate analysis, depth of tumor invasion, pN stage, age, primary location, positive expression of p53, elevated maximal LDH, elevated initial CA19-9 and AFP level were independent prognostic factors for OS. The sMP group had a significantly better OS than dMP group (P = 0.014) in pN0 stage. After further stratification, the survival outcomes were not significantly different between deep muscularis propria tumor invasion without lymph node metastasis (dMPN0) group (stage IB) and superficial muscularis propria tumor invasion with stage 1–2 lymph node metastasis (sMPN1–2) group (stage II) (P = 0.100). Patients with adjuvant chemotherapy had a statistically better survival than those without in dMPN0 group (P = 0.045) and dMPN0 patients with adjuvant chemotherapy had better OS than sMPN1–2 patients (P = 0.015). In addition, greater postoperative survival could be observed in sMPN0 patients than dMPN0 patients in p53-positive group (P = 0.002), and similar OS could be seen between dMPN0 patients with p53-positive and T2N1–2 patients (P = 0.872). Conclusion As a unique subclassification of stage IB GC, appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53, elevated LDH could be potential factors in identifying the different prognoses for stage IB GC patients.

BackgroundBevacizumab has played an important role in the systemic treatment of patients with advanced non-small-cell lung cancer (NSCLC) without gene mutation. In recent years, bevacizumab biosimilar has received marketing approval based on the results of phase III clinical studies. However, more clinical data are needed to verify the efficacy and safety of bevacizumab biosimilar in clinical application.Materials and methodsWe identified 946 patients with locally advanced or metastatic NSCLC who were treated with bevacizumab biosimilar or bevacizumab from January 1, 2019 to November 30, 2021. Comparisons and statistical analyses of bevacizumab biosimilar and bevacizumab were made in terms of efficacy and safety. Efficacy evaluation was performed directly in accordance with RECIST v1.1. Adverse events were graded following the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.ResultsThe objective response rates (ORRs) were 28.9% in the biosimilar group (n=551) and 30.9% in the reference group (n=395; unstratified ORR risk ratio: 0.934, 95% confidence interval [CI]: 0.677–1.138; unstratified ORR risk difference: −0.020, 95% CI: −0.118–0.035). The estimated median progression-free survival (mPFS) were 6.27 (95% CI: 5.53–7.01) and 4.93 (95% CI: 4.24–5.62) months in the biosimilar and reference groups, respectively (P=0.296). The number of treatment lines, combined treatment regimens and with or without radiotherapy were significant factors affecting the PFS of both groups (P

Abstract Background Current treatment options for human epidermal growth factor receptor 2 (HER2)‐overexpressing gastric cancer at third‐line have shown limited clinical benefit. Further, there is no specific treatment for HER2 immunohistochemistry (IHC) 2+ and fluorescence in‐situ hybridization‐negative patients. Here, we report the efficacy and safety of a novel anti‐HER2 antibody RC48 for patients with HER2‐overexpressing, advanced gastric or gastroesophageal junction cancer. Methods Patients with HER2‐overexpressing (IHC 2+ or 3+), locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second‐line therapy were eligible and received RC48 2.5 mg/kg alone every 2 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee. Secondary endpoints included progression‐free survival (PFS), overall survival (OS), duration of response, time to progression, disease control rate, and safety. Results Of 179 patients screened, 125 were eligible and received RC48 treatment. The ORR was 24.8% (95% confidence interval [CI]: 17.5%‐33.3%). The median PFS and OS were 4.1 months (95% CI: 3.7‐4.9 months) and 7.9 months (95% CI: 6.7‐9.9 months), respectively. The most frequently reported adverse events were decreased white blood cell count (53.6%), asthenia (53.6%), hair loss (53.6%), decreased neutrophil count (52.0%), anemia (49.6%), and increased aspartate aminotransferase level (43.2%). Serious adverse events (SAEs) occurred in 45 (36.0%) patients, and RC48‐related SAEs were mainly decreased neutrophil count (3.2%). Seven patients had adverse events that led to death were not RC48‐related. Conclusions RC48 showed promising activity with manageable safety, suggesting potential application in patients with HER2‐overexpressing, advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.

Abstract Rice sheath rot disease caused by Sarocladium oryzae (S. oryzae) infection is an emerging disease, and infection can cause yield losses of 20–85%. Adequate potassium (K) application is a feasible strategy for rice tolerance to S. oryzae infection. However, little is known about the metabolic mechanisms regulated by K that allow rice to cope better with S. oryzae infection. The present study performed a comparative metabolome and transcriptome analysis of rice with different K nutrition statuses before and upon S. oryzae infection. Sarocladium oryzae infection triggered a hydrogen peroxide (H2O2) burst, and K starvation aggravated the accumulation of H2O2 in the flag leaf sheath (FLS), which resulted in lipid peroxidation. Likewise, K deficiency altered the lipid homeostasis of the host plants by hyperaccumulation of 1-alkyl-2-acylglycerophosphoethanolamine. K starvation decreased the content of glycoglycerolipids including monogalactosyldiacyglycerol and digalactosyldoacylglycerol during S. oryzae infection, which destroyed the stability of bilayer membranes. In contrast, sufficient K supply increased antioxidant-related transcript expression (for example, the genes related to glutathione-S-transferase biosynthesis were upregulated), which activated the antioxidant systems. Additionally, upon S. oryzae infection, K starvation amplified the negative impacts of S. oryzae infection on flag leaf photosynthetic potential. These results provide new insight into the role of K in alleviating S. oryzae infection. Adequate K supply decreased the negative impacts of sheath rot disease on rice growth by alleviating lipid peroxidation and maintaining lipid homeostasis.

Traditional electronic medical record systems in hospitals rely on healthcare workers to manually enter patient information, resulting in healthcare workers having to spend a significant amount of time each day filling out electronic medical records. This inefficient interaction seriously affects the communication between doctors and patients and reduces the speed at which doctors can diagnose patients’ conditions. The rapid development of deep learning–based speech recognition technology promises to improve this situation. In this work, we build an online electronic medical record system based on speech interaction. The system integrates a medical linguistic knowledge base, a specialized language model, a personalized acoustic model, and a fault-tolerance mechanism. Hence, we propose and develop an advanced electronic medical record system approach with multi-accent adaptive technology for avoiding the mistakes caused by accents, and it improves the accuracy of speech recognition obviously. For testing the proposed speech recognition electronic medical record system, we construct medical speech recognition data sets using audio and electronic medical records from real medical environments. On the data sets from real clinical scenarios, our proposed algorithm significantly outperforms other machine learning algorithms. Furthermore, compared to traditional electronic medical record systems that rely on keyboard inputs, our system is much more efficient, and its accuracy rate increases with the increasing online time of the proposed system. Our results show that the proposed electronic medical record system is expected to revolutionize the traditional working approach of clinical departments, and it serves more efficient in clinics with low time consumption compared with traditional electronic medical record systems depending on keyboard inputs, which has less recording mistakes and lows down the time consumption in modification of medical recordings; due to the proposed speech recognition electronic medical record system is built on knowledge database of medical terms, so it has a good generalized application and adaption in the clinical scenarios for hospitals.