Impact of R&D innovation and political background on corporate growth: A study based on private listed companies in China.

Based on a review of related concepts and theories this study investigates the different impacts of research and development (R&D) innovation and political background on corporate growth in a particular context. Unlike other studies, we integrate these two factors. We empirically analyze 6079 sets of data from 1292 A-share private manufacturing enterprises in Shanghai and Shenzhen from 2012 to 2019. The results show that these factors directly impact corporate growth and have heterogeneous effects at different enterprise growth levels. We find the effect of R&D innovation on corporate growth is more pronounced for young firms. These findings highlight the need for firms to adjust their investments in R&D innovation and political backgrounds at different stages of development to adapt to different markets and political environments.

Discovery of potential anti- Staphylococcus aureus natural products and their mechanistic studies using machine learning and molecular dynamic simulations.

The structure-activity analysis (SAR) and machine learning were used to investigate potential anti-S. aureus agents in a faster method. In this study, 24 oxygenated benzene ring components with S. aureus inhibition capacity were confirmed by literature exploring and in-house experiments, and the SAR analysis suggested that the hydroxyl group position may affect the anti-S. aureus activity. The 2D-MLR-QSAR model with 9 descriptors was further evaluated as the best model among the 21 models. After that, hesperetic acid and 2-HTPA were further explored and evaluated as the potential anti-S. aureus agents screening in the natural product clustering library through the best QSAR model calculation. The antibacterial capacities of hesperetic acid and 2-HTPA had been investigated and proved the similar predictive pMIC value resulting from the QSAR model. Besides, the two novel components were able to inhibit the growth of S. aureus by disrupting the cell membrane through the molecular dynamics simulation (MD), which further evidenced by scanning electron microscopy (SEM) test and PI dye results. Overall, these results are highly suggested that QSAR can be used to predict the antibacterial agents targeting S. aureus, which provides a new paradigm to research the molecular structure-antibacterial capacity relationship.

Study on multiscale structures and digestibility of cassava starch and medium-chain fatty acids complexes using molecular simulation techniques.

Effect of complexation of three medium-chain fatty acids (octanoic, decylic and lauric acid, OA, DA and LA, respectively) on structural characteristics, physicochemical properties and digestion behaviors of cassava starch (CS) was investigated. Current study indicated that LA was more easily to combine with CS (complex index 88.9%), followed by DA (80.9%), which was also consistent with their corresponding complexed lipids content. Following the investigation of morphology, short-range ordered structure, helical structure, crystalline/amorphous region and fractal dimension of the various complexes, all cassava starch-fatty acids complexes (CS-FAs) were characterized with a flaked morphology rather than a round morphology in native starch (control CS). X-ray diffraction demonstrated that all CS-FAs had a V-type crystalline structure, and nuclear magnetic resonance spectroscopy confirmed that the complexes made from different fatty acids displayed similar V6 or V7 type polymorphs. Interestingly, small-angle X-ray scattering analysis revealed that α value became greater following increased carbon chain length of fatty acids, indicating the formation of a more ordered fractal structure in the aggregates. Changes in rheological parameters G' and G'' indicated that starch complexed with fatty acids was more likely to form a gel network, but difference among three CS-FAs complexes was significant, which might be contributed to their corresponding hydrophobicity and hydrophilicity raised from individual fatty acids. Importantly, digestion indicated that CS-LA complexes had the lowest hydrolysis degree, followed by the greatest RS content, indicating the importance of chain length of fatty acids for manipulating the fine structure and functionality of the complexes.

Exploring the effect of high-pressure processing conditions on the deaggregation of natural major royal jelly proteins (MRJPs) fibrillar aggregates.

High pressure processing is a safe and green novel non-thermal processing technique for modulating food protein aggregation behavior. However, the systematic relationship between high pressure processing conditions and protein deaggregation has not been sufficiently investigated. Major royal jelly proteins, which are naturally highly fibrillar aggregates, and it was found that the pressure level and exposure time could significantly promote protein deaggregation. The 100-200 MPa treatment favoured the deaggregation of proteins with a significant decrease in the sulfhydryl group content. Contrarily, at higher pressure levels (>400 MPa), the exposure time promoted the formation of disordered agglomerates. Notably, the inter-conversion of α-helix and ß-strands in major royal jelly proteins after high pressure processing eliminates the solvent-free cavities inside the aggregates, which exerts a 'collapsing' effect on the fibrillar aggregates. Furthermore, the first machine learning model of the high pressure processing conditions and the protein deaggregation behaviour was developed, which provided digital guidance for protein aggregation regulation.

Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance.

BACKGROUND: The optimal sequential strategy for antibody-drug conjugates (ADCs) in breast cancer remains uncertain. This study aimed to evaluate the efficacy and potential resistance of second ADC (ADC2) following the first ADC (ADC1) in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low MBC. METHODS: This retrospective, multicenter, real-world study enrolled patients with MBC who received at least 2 different types of ADCs in 3 hospitals in China between July 1, 2017 and May 1, 2023. Outcomes included the objective response rate (ORR) for ADC1 and ADC2, progression free survival 2 (PFS2), defined as the time from initiation of ADC2 to progression, and overall survival (OS). RESULTS: Seventy-nine female patients were included, 64 of whom had HER2-positive disease. The ORR for ADC2 with similar payload of ADC1 was found to be 5.3%. When switching to a different payload, the ORR of ADC2 increased to 22.6%. The PFS2 for ADC2 remained similar regardless of whether the payload was similar or different. Switching to different payload showed a higher ORR in patients with rapid progression and a durable response longer than 6 months (41.2% vs 15.0%). Specifically, significantly longer PFS2 and OS were seen in patients treated with trastuzumab deruxtecan (T-Dxd) compared to those treated with disitamab vedotin (RC48) after progression from trastuzumab emtansine (T-DM1; median PFS2 5.37 months vs 3.30 months, HR = 0.40, 95% CI 0.17-0.93, P = .034; median OS 50.6 months vs 20.2 months, HR = 0.27, 95% CI 0.08-0.91, P = .034). For patients who progressed after T-Dxd, the median PFS2 was 6.05 months for those treated with RC48 versus 0.93 months for those treated with T-DM1 (HR = 0.03, 95% CI 0.002-0.353, P = .0093). Genomic analysis revealed that alternation of retinoblastoma1 was significantly associated with superior PFS. CONCLUSION: The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance.

The activation of HAMP promotes colorectal cancer cell proliferation through zinc-mediated upregulation of SMAD4 expression.

Background: Colorectal cancer (CRC) poses a significant challenge in digestive system diseases, and emerging evidence underscores the critical role of zinc metabolism in its progression. This study aimed to investigate the clinical implications of genes at the intersection of zinc metabolism and CRC. Methods: We downloaded CRC prognosis-related genes and zinc metabolism-related genes from public databases. Then, the overlapping genes were screened out, and bioinformatics analysis was performed to obtain the hub gene associated with CRC prognosis. Subsequently, in vitro assays were carried out to investigate the expression of this hub gene and its exact mechanism between zinc metabolism and CRC. Results: HAMP was identified as the hub CRC prognostic gene from overlapping zinc metabolism-related and CRC prognostic genes. In vitro analysis showed HAMP was over-expressed in CRC, and its knockdown inhibited RKO and HCT-116 cell invasion and migration significantly. ZnSO4 induced HAMP up-regulation to promote cell proliferation, while TPEN decreased HAMP expression to inhibit cell proliferation. Importantly, we further found that ZnSO4 enhanced SMAD4 expression to augment HAMP promoter activity and promote cell proliferation in CRC. Conclusions: HAMP stands out as an independent prognostic factor in CRC, representing a potential therapeutic target. Its intricate regulation by zinc, particularly through the modulation of SMAD4, unveils a novel avenue for understanding CRC biology. This study provides valuable insights into the interplay between zinc metabolism, HAMP, and CRC, offering promising clinical indicators for CRC patients. The findings present a compelling case for further exploration and development of targeted therapeutic strategies in CRC management.

A High-Throughput Microdroplet-Based Single Cell Transfection Method for Gene Knockout Based on the CRISPR/Cas9 System.

The efficient application of the newly developed gene-editing method CRISPR/Cas9 requires more accurate intracellular gene delivery. Traditional delivery approaches, such as lipotransfection and non-viral delivery methods, must contend with major problems to overcome the drawbacks of low efficiency, high toxicity, and cell-type dependency. The high-throughput microdroplet-based single-cell transfection method presented herein provides an alternative method for delivering genome-editing reagents into single living cells. By accurately controlling the number of exogenous plasmids in microdroplets, this method can achieve high-efficiency delivery of nucleic acids to different types of single cells. This paper presents a high-throughput quantitative DNA transfection method for single cells and explores the optimal DNA transfection conditions for specific cell lines. The transfection efficiency of cells at different concentrations of DNA in microdroplets is measured. Under the optimized transfection conditions, the method is used to construct gene-knockout cancer cell lines to determine specific gene functions through the CRISPR/Cas9 knockout system. In a case study, the migration ability of TRIM72 knockout cancer cells is inhibited, and the tumorigenicity of cells in a zebrafish tumor model is reduced. A single-cell microfluidic chip is designed to achieve CRISPR/Cas9 DNA transfection, dramatically improving the transfection efficiency of difficult-to-transfect cells. This research demonstrates that the microdroplet method developed herein has a unique advantage in CRISPR/Cas9 gene-editing applications.

Application of virtual diagnosis and treatment combined with medical record teaching method in standardized training of general practitioner.

The aim of this study was to explore the effect of virtual diagnosis and treatment combined with the medical record teaching method in standardized training of general practitioners. Eighty students who had standardized general practice training, from March 2020 to March 2022, in the grassroots practice base of general practitioner training in the affiliated Hospital of our Medical College were retrospectively analyzed and divided into 2 groups according to the teaching method that they received. The differences in assessment scores, critical thinking, clinical thinking ability, learning autonomy ability, and classroom teaching effectiveness were compared, and the students' satisfaction with teaching was investigated. The scores of theoretical knowledge, skill operation, medical history collection, and case analysis in the study group were notably higher (P < .05). In the study group, scores in truth-seeking, openness to knowledge, analytical ability, systematic ability, self-confidence, curiosity, and cognitive maturity were significantly higher (P < .05). A notable improvement was observed in the study group's scores on systematic thinking ability and evidence-based thinking ability, as well as the scores on critical thinking ability after teaching (P < .05). The scores of learning interest, self-management, plan implementation, and cooperation ability improved notably after teaching (P < .05). Learning target, learning processes, learning effects, classroom environment construction, teaching strategy, and technology application in the study group were significantly higher than those in the control group (P < .05). The satisfaction rate in the study group was significantly higher than that in the control group (P < .05). Virtual diagnosis and treatment combined with case-based learning teaching has a very good effect in the standardized training of general practitioners. Students are generally satisfied with their learning experience, which can improve their critical thinking ability and clinical thinking skills. This teaching method is worth further popularizing.

MedChatZH: A tuning LLM for traditional Chinese medicine consultations.

Generative Large Language Models (LLMs) have achieved significant success in various natural language processing tasks, including Question-Answering (QA) and dialogue systems. However, most models are trained on English data and lack strong generalization in providing answers in Chinese. This limitation is especially evident in specialized domains like traditional Chinese medical QA, where performance suffers due to the absence of fine-tuning and high-quality datasets. To address this, we introduce MedChatZH, a dialogue model optimized for Chinese medical QA based on transformer decoder with LLaMA architecture. Continued pre-training on a curated corpus of Chinese medical books is followed by fine-tuning with a carefully selected medical instruction dataset, resulting in MedChatZH outperforming several Chinese dialogue baselines on a real-world medical dialogue dataset. Our model, code, and dataset are publicly available on GitHub (https://github.com/tyang816/MedChatZH) to encourage further research in traditional Chinese medicine and LLMs.

Eosinophilic Gastroenteritis Causing Pyloric Stenosis: A Rare Manifestation.

Eosinophilic gastritis is a gastrointestinal disorder characterized by eosinophilic infiltration in the gastric wall. We present a rare case of critical pyloric stenosis secondary to eosinophilic gastritis in a 16-year-old adolescent girl who presented with nausea, vomiting, early satiety, and abdominal pain. Abdominal computed tomography and subsequent esophagogastroduodenoscopy confirmed the anatomical diagnosis, but histological confirmation of the eosinophilic etiology was challenging. After an unsuccessful trial of high-dose systemic corticosteroids, a laparoscopic gastrojejunostomy was performed and long-term immunosuppression with mycophenolate mofetil was commenced.

Comprehensive Assessment of Posterior Corneal Asphericity Change Calculated by Tangential Radius of Curvature After FS-LASIK and SMILE.

PURPOSE: To evaluate changes in posterior corneal asphericity (ΔQ) using the tangential radius of curvature after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE) procedures. METHODS: One hundred twenty right eyes of myopic patients who underwent either FS-LASIK or SMILE procedures were analyzed using Sirius 3D corneal topography for assessment. The tangential radius was employed to calculate both preoperative and postoperative posterior corneal Q-values across each semimeridian. After both surgical interventions, the ΔQ value variations across the 360° semimeridional regions of the posterior corneal surface were compared. RESULTS: A marked postoperative increase in the posterior corneal Q-value was documented. No significant differences were noted between the postoperative Q-values or ΔQ-values of the two surgical approaches. Among patients with moderate myopia, postoperative Q-value exhibited considerably lower increases and ΔQ-value significantly smaller than their counterparts with high myopia. Moreover, the fluctuation in ΔQ across semimeridional regions was less evident in patients with moderate myopia than in those with high myopia. Notably, the degree of ΔQ fluctuation across semimeridional regions was similar between both surgical categories. These data offer insights into variations in the posterior corneal surface after refractive surgeries depending on the degree of myopia, illuminating their clinical relevance. CONCLUSIONS: Both FS-LASIK and SMILE introduce notable changes to posterior corneal asphericity among patients with different myopia intensities. Furthermore, the influence on the asphericity across the entire posterior surface is similarly distributed between FS-LASIK and SMILE techniques. [J Refract Surg. 2024;40(3):e133-e141.].

Expression and prognostic role of sphingosine 1-phosphate receptor 4 (S1PR4) as a biomarker of skin cutaneous melanoma.

Background: Skin cutaneous melanoma (SKCM) is one of the most lethal skin malignancies worldwide. Sphingosine 1-phosphate (S1P) regulates tumor cells through S1P receptors (S1PRs). Unlike S1PR1/2/3/5, whose anti-apoptotic effects have been widely studied, the regulatory effect of S1PR4 on tumors has not been studied extensively. In this study, we aimed to investigate the correlation between S1PR4 expression and survival, clinical manifestations, tumor microenvironment, and immune infiltration in patients with SKCM. Results: Low S1PR4 expression was associated with poor prognosis in patients with SKCM. Patients in the high-expression group had significantly longer disease survival and progression-free survival than those in the low-expression group. Conclusion: High S1PR4 expression was highly associated with better prognosis and milder clinical manifestations; thus, S1PR4 may be used as a prognostic marker to help physicians monitor patients with SKCM.

Metal-organic frameworks with fine-tuned interlayer spacing for microwave absorption.

Designing a functional, conductive metal-organic framework (cMOF) is highly desired. Substantial efforts have been dedicated to increasing the intralayer conjugation of the cMOFs, while less dedication has been made to tuning the interlayer charge transport of the metal-organic nanosheets for the controllable dielectric property. Here, we construct a series of conductive bimetallic organic frameworks of (ZnxCu3-x) (hexahydroxytriphenylene)2 (ZnCu-HHTP) to allow for fine-tuned interlayer spacing of two-dimensional frameworks, by adjusting the ratios of Zn and Cu metal ions. This approach for atomistic interlayer design allows for the finely control of the charge transport, band structure, and dielectric properties of the cMOF. As a result, Zn3Cu1-HHTP, with an optimal dielectric property, exhibits high-efficiency absorption in the gigahertz microwave range, achieving an ultra-strong reflection loss of -81.62 decibels. This study not only advances the understanding of the microstructure-function relationships in cMOFs but also offers a generic nanotechnology-based approach to achieving controllable interlayer spacing in MOFs for the targeted applications.

Inhibitory effects of nobiletin-mediated interfacial instability of bile salt emulsified oil droplets on lipid digestion.

Previous lipase inhibitors studies mainly focus on the binding between inhibitors and lipase, ignoring the impact of inhibitors on the oil-water interface of lipid droplets. This study aimed to investigate the effect of nobiletin (NBT) from Citri Reticulatae Pericarpium on the oil-water interface properties and lipid digestion. Here, we found that NBT could destroy bile salt (BS)-stabilized lipid droplets and thus inhibited free fatty acid release, owing to the interaction between NBT and BS at the oil-water interface, and reducing the stability of the oil-water interface (the stability index decreased from 91.15 ± 2.6 % to 66.5 ± 3.6 %). Further, the molecular dynamics simulation and isothermal titration calorimetry revealed that NBT could combine with BS at oil-water interface through intermolecular interactions, including hydrogen bonds, Van der Waals force, and steric hindrance. These results suggest that the interfacial instability of NBT mediated BS emulsified oil droplets may be another pathway to inhibit lipid digestion.

Visible light-promoted difluoromethylthiolation of cycloalkanols by C-C bond cleavage.

A mild and general methodology for the difluoromethylthiolation of cycloalkanols has been developed by employing N-difluoromethylthiophthalimide as the SCF2H radical source, in combination with an acridinium-derived organo-photosensitizer, under redox-neutral conditions. This reaction protocol demonstrates high efficiency, scalability, and mild reaction conditions, thus presenting a green approach for the rapid synthesis of distal difluoromethylthiolated alkyl ketones that are challenging to be synthesized through alternative means.

Sleep deprivation-induced anxiety-like behaviors are associated with alterations in the gut microbiota and metabolites.

The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance (P = 0.0002) and staying time in the central zone (P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine (P = 0.018) and tryptophan (P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila, Muribaculum intestinale, and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS (P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation. IMPORTANCE: The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.

In Silico Prediction of Chemical Acute Dermal Toxicity Using Explainable Machine Learning Methods.

The research on acute dermal toxicity has consistently been a crucial component in assessing the potential risks of human exposure to active ingredients in pesticides and related plant protection products. However, it is difficult to directly identify the acute dermal toxicity of potential compounds through animal experiments alone. In our study, we separately integrated 1735 experimental data based on rabbits and 1679 experimental data based on rats to construct acute dermal toxicity prediction models using machine learning and deep learning algorithms. The best models for the two animal species achieved AUC values of 78.0 and 82.0%, respectively, on 10-fold cross-validation. Additionally, we employed SARpy to extract structural alerts, and in conjunction with Shapley additive explanation and attentive FP heatmap, we identified important features and structural fragments associated with acute dermal toxicity. This approach offers valuable insights for the detection of positive compounds. Moreover, a standalone software tool was developed to make acute dermal toxicity prediction easier. In summary, our research would provide an effective tool for acute dermal toxicity evaluation of pesticides, cosmetics, and drug safety assessment.

One-step strategy for efficient Cr(VI) removal via phytate modified zero-valent iron: Accelerated electron transfer and enhanced coordination effect.

The toxic Cr(VI) from industrial wastewater pose serious threat to the human beings and eco-systems. To reduce the operation processes and enhance the removal efficiency of Cr(VI), targeted design of functionalized material is critical in practical applications. Herein, we developed a one-step strategy for simultaneous Cr(VI) reduction and total Cr capture by a novel phytate modified zero-valent iron (PA-ZVI). The reaction kinetics of Cr(VI) removal by PA-ZVI (0.2225 min-1) was 53 times higher compared to ZVI (0.0042 min-1). The Fe(0) content on the surface of PA-ZVI increased from 2.2% to 15.6% compared to ZVI. Meanwhile, Cr(VI) was liable to adsorb on the surface of PA-ZVI due to its lower adsorption energy compared with the original ZVI (-2.09 eV vs -0.85 eV). The incorporation of the phytate ligand promoted electron transfer from iron core to Cr(VI), leading to the rapid in-situ reduction of Cr(VI) adsorbed on the surface of PA-ZVI to Cr(III). PA-ZVI exhibited a satisfactory performance for Cr(VI) removal at a broad pH range (3-11) and in the presence of coexisting ions and humic acid. Moreover, the reactor with the addition of PA-ZVI achieved more than 90% Cr(VI) removal within 72 h in continuous flow experiments. The feasibility of PA-ZVI for the removal of Cr(VI) is also validated in authentic wastewater. This work provides novel ZVI materials that can effectively address decontamination challenges from Cr(VI) pollution.

Teleoperation of an Anthropomorphic Robot Hand with a Metamorphic Palm and Tunable-Stiffness Soft Fingers.

Teleoperation in soft robotics can endow soft robots with the ability to perform complex tasks through human-robot interaction. In this study, we propose a teleoperated anthropomorphic soft robot hand with variable degrees of freedom (DOFs) and a metamorphic palm. The soft robot hand consists of four pneumatic-actuated fingers, which can be heated to tune stiffness. A metamorphic mechanism was actuated to morph the hand palm by servo motors. The human fingers' DOF, gesture, and muscle stiffness were collected and mapped to the soft robotic hand through the sensory feedback from surface electromyography devices on the jib. The results show that the proposed soft robot hand can generate a variety of anthropomorphic configurations and can be remotely controlled to perform complex tasks such as primitively operating the cell phone and placing the building blocks. We also show that the soft hand can grasp a target through the slit by varying the DOFs and stiffness in a trail.

Antibacterial Effect of Sesame Protein-Derived Peptides against Escherichia coli and Staphylococcus aureus: In Silico and In Vitro Analysis.

This study aimed to screen out antibacterial peptides derived from sesame (Sesamum indicum L.) through in silico and in vitro methods. In silico proteolysis of sesame proteins with pepsin, trypsin, and chymotrypsin was performed with the online server BIOPEP-UWM. The CAMPR3 online server was used to predict the antimicrobial effect of peptides. The ToxinPred, PepCalc, and AllergenFP tools were utilized to forecast the physicochemical properties, toxicity, and allergen of the peptides. Molecular docking analysis showed that six cationic antimicrobial peptides could directly interact with the key sites of dihydropteroate synthase, whereas Ala-Gly-Gly-Val-Pro-Arg and Ser-Thr-Ile-Arg exhibited the strongest binding affinity. In vitro antibacterial experiment showed the minimum inhibitory concentration (MIC) of Ser-Thr-Ile-Arg against Escherichia coli and Staphylococcus aureus was 1024 and 512 µg/mL, respectively. Meanwhile, MIC of Ala-Gly-Gly-Val-Pro-Arg against both bacterial species was 512 µg/mL. Our results suggest that peptides from sesame possess the ability to potentially hinder bacterial activity.