Impact of Sacrificial Hydrogen Bonds on the Structure and Properties of Rubber Materials: Insights from All-Atom Molecular Dynamics Simulations.

The inclusion of sacrificial hydrogen bonds is crucial for advancing high-performance rubber materials. However, the molecular mechanisms governing the impact of these bonds on material properties remain unclear, hindering progress in advanced rubber material research. This study employed all-atom molecular dynamics simulations to thoroughly investigate how hydrogen bonds affect the structure, dynamics, mechanics, and linear viscoelasticity of rubber materials. As the modified repeating unit ratio (ß) increased, both interchain and intrachain hydrogen bond content rose, with interchain bonds playing a predominant role. This physical cross-linking network formed through interchain hydrogen bonds restricts molecular chain movement and relaxation and raises the glass transition temperature of rubber. Within a certain content of hydrogen bonds, the mechanical strength increases with increasing ß. However, further increasing ß leads to a subsequent decrease in the mechanical performance. Optimal mechanical properties were observed at ß = 6%. On the other hand, a higher ß value yields an elevated stress relaxation modulus and an extended stress relaxation plateau, signifying a more complex hydrogen-bond cross-linking network. Additionally, higher ß increases the storage modulus, loss modulus, and complex viscosity while reducing the loss factor. In summary, this study successfully established the relationship between the structure and properties of natural rubber containing hydrogen bonds, providing a scientific foundation for the design of high-performance rubber materials.

Use of Reverse Shock Index Multiplied by Simplified Motor Score in a Five-Level Triage System: Identifying Trauma in Adult Patients at a High Risk of Mortality.

Background and Objectives: The Taiwan Triage and Acuity Scale (TTAS) is reliable for triaging patients in emergency departments in Taiwan; however, most triage decisions are still based on chief complaints. The reverse-shock index (SI) multiplied by the simplified motor score (rSI-sMS) is a more comprehensive approach to triage that combines the SI and a modified consciousness assessment. We investigated the combination of the TTAS and rSI-sMS for triage compared with either parameter alone as well as the SI and modified SI. Materials and Methods: We analyzed 13,144 patients with trauma from the Taipei Tzu Chi Trauma Database. We investigated the prioritization performance of the TTAS, rSI-sMS, and their combination. A subgroup analysis was performed to evaluate the trends in all clinical outcomes for different rSI-sMS values. The sensitivity and specificity of rSI-sMS were investigated at a cutoff value of 4 (based on previous study and the highest score of the Youden Index) in predicting injury severity clinical outcomes under the TTAS system were also investigated. Results: Compared with patients in triage level III, those in triage levels I and II had higher odds ratios for major injury (as indicated by revised trauma score < 7 and injury severity score [ISS] ≥ 16), intensive care unit (ICU) admission, prolonged ICU stay (≥14 days), prolonged hospital stay (≥30 days), and mortality. In all three triage levels, the rSI-sMS < 4 group had severe injury and worse outcomes than the rSI-sMS ≥ 4 group. The TTAS and rSI-sMS had higher area under the receiver operating characteristic curves (AUROCs) for mortality, ICU admission, prolonged ICU stay, and prolonged hospital stay than the SI and modified SI. The combination of the TTAS and rSI-sMS had the highest AUROC for all clinical outcomes. The prediction performance of rSI-sMS < 4 for major injury (ISS ≥ 16) exhibited 81.49% specificity in triage levels I and II and 87.6% specificity in triage level III. The specificity for mortality was 79.2% in triage levels I and II and 87.4% in triage level III. Conclusions: The combination of rSI-sMS and the TTAS yielded superior prioritization performance to TTAS alone. The integration of rSI-sMS and TTAS effectively enhances the efficiency and accuracy of identifying trauma patients at a high risk of mortality.

Bio-Based Copolyester PEIFT: Enhanced Hydrophilicity, Rigidity, and Applications in Nanofibers.

The raw materials of Poly(ethylene terephthalate) (PET) are derived from petroleum-based resources, which are no sustainable. Therefore, previous researchers introduced biomass-derived 2,5-tetrahydrofurfuryl dimethanol (THFDM) into PET. However, its heat resistance has decreased compared to PET. In this paper, a novel bio-based copolyester, poly(ethylene glycol-co-2,5-tetrahydrofuran dimethanol-co-isosorbide terephthalate) (PEIFT), is prepared by introducing biomass-derived isosorbide (ISB) and THFDM into the PET chains through melting copolymerization process. With the introduction of ISB content, copolyesters' hydrophilicity and rigidity improve. Compared to PET, glass transition temperature (Tg) increases by over 5 °C. In addition, the toughness and spinning performance of PEIFT have also been improved as a result of the addition of THFDM components. The hydrophobicity of PEIFTs electrospinning is greatly improved, with a contact angle exceeding 135°. Finally, due to the good hydrophobicity of PEIFTs nanofibers, they have potential application value in the manufacture of hydrophobic nanofiber and filter films. Given its biomass source and excellent performance, they make it easier to replace materials derived from petroleum.

Air-Stable Self-Driven UV Photodetectors on Controllable Lead-Free CsCu2I3 Microwire Arrays.

The rapid evolution of the Internet of Things has engendered increased requirements for low-cost, self-powered UV photodetectors. Herein, high-performance self-driven UV photodetectors are fabricated by designing asymmetric metal-semiconductor-metal structures on the high-quality large-area CsCu2I3 microwire arrays. The asymmetrical depletion region doubles the photocurrent and response speed compared to the symmetric structure device, leading to a high responsivity of 233 mA/W to 355 nm radiation. Notably, at 0 V bias, the asymmetric device produces an open-circuit voltage of 356 mV and drives to a short-circuit current of 372 pA; meanwhile, the switch ratio (Iph/Idark) reaches up to 103, indicating its excellent potential for detecting weak light. Furthermore, the device maintains stable responses throughout 10000 UV-light switch cycles, with negligible degradation even after 90-day storage in air. Our work establishes that CsCu2I3 is a good candidate for self-powered UV detection and thoroughly demonstrates its potential as a passive device.

[Liujunzi Decoction treats 4NQO-induced esophageal cancer in mice: a study based on serum metabolomics].

This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 µg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.

Microbial metabolism of diosgenin by a novel isolated Mycolicibacterium sp. HK-90: A promising biosynthetic platform to produce 19-carbon and 21-carbon steroids.

Green manufacture of steroid precursors from diosgenin by microbial replacing multistep chemical synthesis has been elusive. It is currently limited by the lack of strain and degradation mechanisms. Here, we demonstrated the feasibility of this process using a novel strain Mycolicibacterium sp. HK-90 with efficiency in diosgenin degradation. Diosgenin degradation by strain HK-90 involves the selective removal of 5,6-spiroketal structure, followed by the oxygenolytic cleavage of steroid nuclei. Bioinformatic analyses revealed the presence of two complete steroid catabolic gene clusters, SCG-1 and SCG-2, in the genome of strain HK-90. SCG-1 cluster was found to be involved in classic phytosterols or cholesterol catabolic pathway through the deletion of key kstD1 gene, which promoted the mutant m-∆kstD1 converting phytosterols to intermediate 9α-hydroxyandrostenedione (9-OHAD). Most impressively, global transcriptomics and characterization of key genes suggested SCG-2 as a potential gene cluster encoding diosgenin degradation. The gene inactivation of kstD2 in SCG-2 resulted in the conversion of diosgenin to 9-OHAD and 9,16-dihydroxy-pregn-4-ene-3,20-dione (9,16-(OH)2 -PG) in mutant m-ΔkstD2. Moreover, the engineered strain mHust-ΔkstD1,2,3 with a triple deletion of kstDs was constructed, which can stably accumulate 9-OHAD by metabolizing phytosterols, and accumulate 9-OHAD and 9,16-(OH)2 -PG from diosgenin. Diosgenin catabolism in strain mHust-ΔkstD1,2,3 was revealed as a progression through diosgenone, 9,16-(OH)2 -PG, and 9-OHAD to 9α-hydroxytestosterone (9-OHTS). So far, this work is the first report on genetically engineered strain metabolizing diosgenin to produce 21-carbon and 19-carbon steroids. This study presents a promising biosynthetic platform for the green production of steroid precursors, and provide insights into the complex biochemical mechanism of diosgenin catabolism.

Let-7b-5p promotes triptolide-induced growth-inhibiting effects in glioma by targeting IGF1R.

Glioma is one of the most common malignancies of the central nervous system. The therapeutic effect has not been satisfactory despite advances in comprehensive treatment techniques. Our previous studies have found that triptolide inhibits glioma proliferation through the ROS/JNK pathway, but in-depth mechanisms need to be explored. Recent studies have confirmed that miRNAs may function as tumor suppressor genes or oncogenes and be involved in cancer development and progression. In this study, we found that let-7b-5p expression levels closely correlated with WHO grades and overall survival in patients in tumor glioma-CGGA-mRNAseq-325, and the upregulation of let-7b-5p can inhibit the proliferation and induce apoptosis of glioma cells. Functionally, upregulation of let-7b-5p increased the inhibitory effect on cell viability and colony formation caused by triptolide and promoted the apoptosis rate of triptolide-treated U251 cells. Conversely, downregulation of let-7b-5p had the opposite effect, indicating that let-7b-5p is a tumor suppressor miRNA in glioma cells. Moreover, target prediction, luciferase reporter assays and functional experiments revealed that IGF1R was a direct target of let-7b-5p. In addition, upregulation of IGF1R reversed the triptolide-regulated inhibition of cell viability but promoted glioma cell apoptosis and activated the ROS/JNK signaling pathway induced by triptolide. The results obtained in vivo experiments substantiated those from the in vitro experiments. In summary, the current study provides evidence that triptolide inhibits the growth of glioma cells by regulating the let-7b-5p-IGF1R-ROS/JNK axis in vitro and in vivo. These findings may provide new ideas and potential targets for molecularly targeted therapies for comprehensive glioma treatment.

Effect of plasma-activated lactic acid on microbiota composition and quality of puffer fish (Takifugu obscurus) fillets during chilled storage.

Fresh puffer fish (Takifugu obscurus) are susceptible to microbial contamination and have a very short shelf-life of chilled storage. Hence, this study aimed to evaluate the effects of plasma-activated lactic acid (PALA) on microbiota composition and quality attributes of puffer fish fillets during chilled storage. The results showed that PALA treatment effectively reduced the growth of bacteria and attenuated changes in physicochemical indicators (total volatile basic nitrogen, pH value, K value, and biogenic amines) of puffer fish fillets. Additionally, insignificant changes were observed in lipid oxidation during the first 8 days (p > 0.05). Illumina-MiSeq high-throughput sequencing revealed that PALA effectively inhibited the growth of Pseudomonas in puffer fish fillets and maintained the diverse characteristics of the microbial community. In combination with sensory analysis, PALA extended the shelf life of puffer fish fillets for 4 days, suggesting that PALA could be considered a potential fish fillet preservation method.

Predictive factors that influence the clinical efficacy of umbilical cord-derived mesenchymal stromal cells in the treatment of type 2 diabetes mellitus.

BACKGROUND: Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint. METHODS: In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed. RESULTS: At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels. CONCLUSIONS: Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion.

Intraparticle sorption and desorption of antibiotics.

Intraparticle domains are the critical locations for storing contaminants and retarding contaminant transport in subsurface environments. While the kinetics and extent of antibiotics sorption and desorption in subsurface materials have been extensively studied, their behaviors in intraparticle domains have not been well understood. This study investigated the sorption and desorption of antibiotics (ATs) in the intraparticle domains using quartz grains and clay, and antibiotic tetracycline (TC) and levofloxacin (LEV) as examples that are commonly present in groundwater systems. Batch experiments coupled with the analyses using various microscopic and spectroscopic techniques were performed to investigate the sorption and desorption kinetics, and to provide insights into the intraparticle sorption and desorption of TC and LEV. Results indicated that both TC and LEV with different physiochemical properties can migrate into intraparticle domains that were consistent with sorptive diffusion. The rate and extent of the sorption are a function of intraparticle surface area and properties, pore volume and connectivity, and ionic properties of the ATs. The sorptive diffusion led to the slow desorption of both TC and LEV after their sorption, apparently showing an irreversible desorption behavior (with desorption percentage about 1.86-20.51%). These results implied that intraparticle domains can be important locations for storing ATs, retarding ATs transport, and may serve as a long-term secondary source for groundwater contamination.

Coral-like CoSe2@N-doped carbon with a high initial coulombic efficiency as advanced anode materials for Na-ion batteries.

Na-ion batteries (NIBs) have attracted great interest as a possible technology for grid-scale energy storage for the past few years owing to the wide distribution, low cost and environmental friendliness of sodium resources and similar chemical mechanisms to those of established Li-ion batteries (LIBs). Nonetheless, the implementation of NIBs is seriously hindered because of their low rate capability and cycling stability. This is mainly because the large ionic size of Na+ can reduce the structural stability and cause sluggish reaction kinetics of electrode materials. Herein, three-dimensional nanoarchitectured coral-like CoSe2@N-doped carbon (CL-CoSe2@NC) was synthesized through solvothermal and selenizing techniques. As a result, CL-CoSe2@NC for NIBs at 2 A g-1 exhibits an ultrahigh specific capacity of 345.4 mA h g-1 after 2800 cycles and a superhigh initial coulombic efficiency (ICE) of 93.1%. Ex situ XRD, HRTEM, SAED and XPS were executed to study the crystal structure evolution between Na and CoSe2 during sodiation/de-sodiation processes. The aforementioned results indicate that the improved sodium storage property of CL-CoSe2@NC could be attributed to better electrode kinetics and a stable SEI film because of the 3D nanoarchitecture and the existence of the NC layer.

Effect of runx2b deficiency in intermuscular bones on the regulatory network of lncRNA-miRNA-mRNA.

Intermuscular bones (IBs) are mineralized spicules that negatively impact the quality and value of fish products. Runx2b is a crucial modulator in promoting bone formation through regulating osteoblast differentiation. Previous studies suggested that loss of runx2b gene completely inhibited IBs formation in zebrafish. However, how the whole transcriptome, including mRNA and non-coding RNA (ncRNA), affects the IBs development in runx2b-/- zebrafish are not known. The aim of this study was to identify the regulatory networks of differentially expressed (DE) lncRNAs, miRNAs, and mRNAs in zebrafish with and without IBs (runx2b+/+ fish and runx2b-/- fish) utilizing high-throughput sequencing techniques. All together there are 1051 mRNAs, 456 lncRNAs, and 18 miRNAs differentially expressed were found between these two strains. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) has highlighted significant pathways linked to the development of IBs, specifically the TGF-beta and Wnt signaling pathways, and a number of genes concentrated on these two signaling pathways related to the formation of IBs. Further, 1989 competing endogenous RNA (ceRNA) networks were created according to the correlation among mRNAs, miRNAs and lncRNAs. The ceRNA networks results revealed 52 ceRNA pairs related to the IBs formation, consisting of 52 mRNAs, 37 lncRNAs, and 6 miRNAs. Of these, we found that dre-miR-2189 was the key element of ceRNA pairs, interacting with 19 mRNAs and 11 lncRNAs, and MSTRG.13175.1 could regulate sp7 expression by interacting with dre-miR-2189 to function in osteogenic differentiation. Subsequent experiments at the cellular level also revealed the interaction mechanism. The outcomes indicated a crucial role of miRNAs and lncRNAs in the development of fish IBs, which offer new views into the functions of ncRNAs involved in IBs formation.

Advances in the phytochemistry and pharmacology of plant-derived phthalides.

Phthalides are a class of unique compounds such as ligustilide, butylphthalide and butyldenephthalide, which have shown to possess multiple bioactivities in new drug research and development. Phthalides are naturally distributed in different plants that have been utilized as herbal treatments for various ailments with a long history in Asia, Europe and North America. Their extensive biological activity has led to a dramatic increase in the study of phthalide compounds in recent years. This review summarizes the latest research progress of plant-derived phthalides, and a total of 133 phthalide compounds are described based on the characteristics of chemical structures. Pharmacological properties of plant-derived phthalides are associated with hemorheological improvement, vascular function modulation and central nervous system protection. Potential treatments for a variety of diseases mainly including cardio-cerebrovascular disorders and neurological complications such as Alzheimer's disease are also concluded. In addition, key metabolic pathways have been clearly elucidated. Further investigations on the molecular mechanisms involved in biological activity are recommended for offering new insights into profound comprehension of phthalide applications.

Predicted superconductivity in one-dimensional A3Hf2B3-type electrides.

Inorganic electrides are considered potential superconductors due to the unique properties of their anionic electrons. However, most electrides require external high-pressure conditions to exhibit considerable superconducting transition temperatures (Tc). Therefore, searching for superconducting electrides under low or moderate external pressures is of significant research interest and importance. In this work, a series of A3Hf2B3-type compounds (A = Mg, Ca, Sr, Ba; B = Si, Ge, Sn, Pb) were constructed and systematically studied based on density functional theory calculations. According to the analysis of the electronic structures and phonon dispersion spectrums, stable one-dimensional electrides Ca3Hf2Ge3, Ca3Hf2Sn3, and Sr3Hf2Pb3, were screened out. Interestingly, the superconductivity of these electrides were predicted from electron phonon coupling calculations. It is highlighted that Sr3Hf2Pb3 showed the highest Tc, reaching 4.02 K, while the Tc values of Ca3Hf2Ge3 and Ca3Hf2Sn3 were 1.16 K and 1.04 K, respectively. Moreover, the Tc value of Ca3Hf2Ge3 can be increased to 1.96 K under 20 GPa due to the effect of phonon softening. This work enriches the types of superconducting electrides and has important guiding significance for the research on constructing electrides and related superconducting materials.

HPLC for simultaneous quantification of free mannose and glucose concentrations in serum: use in detection of ovarian cancer.

Background: Abnormal levels of monosaccharides in blood have been linked to tumorigenesis. In this study, a novel high-performance liquid chromatography (HPLC) method was established for the simultaneous determination of free mannose and glucose in the serum. Methods: The serum was directly derivatized by 1-phenyl-3-methyl-5-pyrazolone under alkaline conditions using L-rhamnose as an internal standard. The chromatographic separation was then performed on a Poroshell EC-C18 chromatographic column (4.6 × 100 mm, particle size 2.7 µm, Agilent) with gradient elution using NH4Ac-HAc and acetonitrile as the mobile phases. The method was thereafter validated according to international guidelines. The serum samples obtained from 200 healthy individuals and 200 ovarian cancer (OC) patients were analyzed for free mannose and glucose. Results: The method was found to be reproducible for quantification within 20 min and included online sample purification. The method displayed excellent linearity in the concentration range (for mannose: 0.5-500 µg/mL; glucose: 0.5-1500 µg/mL). The precision, recovery, and stability met the FDA bioanalytical method validation acceptance criteria. Overall, the measurement of glucose content by HPLC correlated well with the different enzymatic methods. Ovarian cancer mannose levels in the serum were significantly higher in the advanced stage (61.22 µmol/L, p < 0.0001) than those in healthy volunteers and early-stage patients (44.51 µmol/L versus 50.09 µmol/L, p < 0.0001). The AUC for the ratio of serum free glucose to mannose (G/M) was 0.98 (p < 0.0001), with a sensitivity of 91.46% and a specificity of 98.50%, which served as a biomarker for OC diagnosis. Conclusion: We report a simple, repeatable, and attractive analytical method by HPLC, which can be used for quantitative estimation of free mannose and glucose simultaneously in human serum. Our results indicate that the serum level of mannose could be used as a potential biomarker of ovarian cancer.

A Ten-Year Retrospective Cohort Study on Neck Collar Immobilization in Trauma Patients with Head and Neck Injuries.

Background and Objectives: In the context of prehospital care, spinal immobilization is commonly employed to maintain cervical stability in head and neck injury patients. However, its use in cases of unclear consciousness or major trauma patients is often precautionary, pending the exclusion of unstable spinal injuries through appropriate diagnostic imaging. The impact of prehospital C-spinal immobilization in these specific patient populations remains uncertain. Materials and Methods: We conducted a retrospective cohort study at Taipei Tzu Chi Hospital from January 2009 to May 2019, focusing on trauma patients suspected of head and neck injuries. The primary outcome assessed was in-hospital mortality. We employed multivariable logistic regression to investigate the relationship between prehospital C-spine immobilization and outcomes, while adjusting for various factors such as age, gender, type of traumatic brain injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and activation of trauma team. Results: Our analysis encompassed 2733 patients. Among these, patients in the unclear consciousness group (GCS ≤ 8) who underwent C-spine immobilization exhibited a higher mortality rate than those without immobilization. However, there was no statistically significant difference in mortality among patients with alert consciousness (GCS > 8). Multivariable logistic regression analysis revealed that advanced age (age ≥ 65), unclear consciousness (GCS ≤ 8), major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and the use of neck collars for immobilization (adjusted OR: 1.850, 95% CI: 1.240-2.760, p = 0.003) were significantly associated with an increased risk of mortality. Subgroup analysis indicated that C-spine immobilization was significantly linked to an elevated risk of mortality in older adults (age ≥ 65), patients with unclear consciousness (GCS ≤ 8), those with major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and individuals in shock (shock index > 1). Conclusions: While our findings do not advocate for the complete abandonment of neck collars in all suspected head and neck injury patients, our study suggests that prehospital cervical and spinal immobilization should be applied more selectively in certain head and neck injury populations. This approach is particularly relevant for older individuals (age ≥ 65), those with unclear consciousness (GCS ≤ 8), individuals experiencing major traumatic injuries (ISS ≥ 16 or RTS ≤ 7), and patients in a state of shock (shock index ≥ 1). Our study employs a retrospective cohort design, which may introduce selection bias. Therefore, in the future, there is a need for confirmation of our results through a two-arm randomized controlled trial (RCT) arises, as this design is considered ideal for addressing this issue.

A gene expression profile-based approach to screen the occurrence and predisposed host characteristics of drug-induced liver injury: a case study of Psoralea corylifolia Linn.

Drug-induced liver injury (DILI) is one of the most common causes of a drug being withdrawn, and identifying the culprit drugs and the host factors at risk of causing DILI has become a current challenge. Recent studies have found that immune status plays a considerable role in the development of DILI. In this study, DILI-related differentially expressed genes mediated by immunoinflammatory cytokines were obtained from the Gene Expression Omnibus (GEO) database to predict the occurrence of DILI (named the DILI predictive gene set, DILI_PGS), and the predictability of the DILI_PGS was verified using the Connectivity Map (CMap) and LiverTox platforms. The results obtained DILI_PGS from the GEO database could predict 81.25% of liver injury drugs. In addition, the Coexpedia platform was used to predict the DILI_PGS-related characteristics of common host diseases and found that the DILI_PGS mainly involved immune-related diseases and tumor-related diseases. Then, animal models of immune stress (IS) and immunosuppressive (IP) were selected to simulate the immune status of the above diseases. Meanwhile, psoralen, a main component derived from Psoralea corylifolia Linn. with definite hepatotoxicity, was selected as an experimental drug with highly similar molecular fingerprints to three idiosyncratic hepatotoxic drugs (nefazodone, trovafloxacin, and nimesulide) from the same DILI_PGS dataset. The animal experiment results found a single administration of psoralen could significantly induce liver injury in IS mice, while there was no obvious liver function change in IP mice by repeatedly administering the same dose of psoralen, and the potential mechanism of psoralen-induced liver injury in IS mice may be related to regulating the expression of the TNF-related pathway. In conclusion, this study constructed the DILI_PGS with high accuracy to predict the occurrence of DILI and preliminarily identified the characteristics of host factors inducing DILI.

Neoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in resectable non-small cell lung cancer.

Background: Neoadjuvant immunotherapy, the focus of current research and treatment modality for long-term survival, has become one of the main options in supporting primary treatment interventions in early NSCLC. Methods: This was a retrospective analysis of patients with locally resectable NSCLC who received the neoadjuvant drug pembrolizumab combined with chemotherapy and underwent surgical resection. Pathological responses, PFS and OS in the whole sample and subgroups were analyzed. Results: Of the 61 patients included in this retrospective analysis, 31 (50.82%) achieved a pCR, and 38 (62.30%) obtained an MPR. Patients with a pCR had significantly higher OS than the non-pCR group (HR = 0.093, P = 0.0227); patients with an MPR also had significantly elevated OS compared with the non-MPR group (HR = 0.05357, P = 0.0169). Patients with lymph node metastasis after surgery had significantly reduced OS (HR = 0.01607, p = 0.0004) and PFS (HR = 0.08757, p = 0.0004) than those without lymph node metastasis. There was no significant difference in OS and PFS between squamous cell carcinomas (SCC) group and adenocarcinomas (AD) group. No significant differences in OS and PFS were found between patients administered 2 and 3 cycles of neoadjuvant therapy before surgery, between those administered ≤5 and > 5 cycles of adjuvant therapy post-surgery, and between patients with TPS <50% and ≥50% (all P > 0.05). Conclusion: Neoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in non-small cell lung cancer is safe and tolerable. Both pCR and MPR were closely associated with OS and PFS, reflecting a good response of tumor tissues to drug therapy. Lymph node metastasis after surgery was a poor prognostic factor, reducing OS and PFS.

Life-course social disparities in body mass index trajectories across adulthood: cohort study evidence from China health and nutrition survey.

BACKGROUND: The social disparities in obesity may originate in early life or in adulthood, and the associations of socioeconomic position (SEP) with obesity could alter over time. It is unclear how lifetime-specific and life-course SEP influence adult obesity development in China. METHODS: Based on the China Health and Nutrition Survey (CHNS), three SEP-related indicators, including the father's occupational position and the participant's education and occupational position, were obtained. The life-course socioeconomic changes and a cumulative SEP score were established to represent the life-course SEP of the participants in the study. The growth mixture modeling was used to identify BMI trajectories in adulthood. Multinomial logistic regression was adopted to assess the associations between SEP and adult BMI trajectories. RESULTS: A total of 3,138 participants were included in the study. A positive correlation was found between the paternal occupational position, the participants' occupational position, education, and obesity in males, whereas an inverse correlation was observed among females. Males who experienced social upward mobility or remained stable high SEP during the follow-up had 2.31 and 2.52-fold risks of progressive obesity compared to those with a stable-low SEP. Among females, stable high SEP in both childhood and adulthood was associated with lower risks of progressive obesity (OR = 0.63, 95% CI: 0.43-0.94). Higher risks of obesity were associated with the life-course cumulative SEP score among males, while the opposite relationship was observed among females. CONCLUSIONS: The associations between life-course SEP and BMI development trajectories differed significantly by gender. Special emphasis should be placed on males experiencing upward and stable high socioeconomic change.

Drug repurposing based on the similarity gene expression signatures to explore for potential indications of quercetin: a case study of multiple sclerosis.

Quercetin (QR) is a natural flavonol compound widely distributed in the plant kingdom with extensive pharmacological effects. To find the potential clinical indications of QR, 156 differentially expressed genes (DEGs) regulated by QR were obtained from the Gene Expression Omnibus database, and new potential pharmacological effects and clinical indications of QR were repurposed by integrating compounds with similar gene perturbation signatures and associated-disease signatures to QR based on the Connectivity Map and Coexpedia platforms. The results suggested QR has mainly potential therapeutic effects on multiple sclerosis (MS), osteoarthritis, type 2 diabetes mellitus, and acute leukemia. Then, MS was selected for subsequent animal experiments as a representative potential indication, and it found that QR significantly delays the onset time of classical MS model animal mice and ameliorates the inflammatory infiltration and demyelination in the central nervous system. Combined with network pharmacology technology, the therapeutic mechanism of QR on MS was further demonstrated to be related to the inhibition of the expression of inflammatory cytokines (TNF-α, IL-6, IL-1ß, IFN-γ, IL-17A, and IL-2) related to TNF-α/TNFR1 signaling pathway. In conclusion, this study expanded the clinical indications of QR and preliminarily confirmed the therapeutic effect and potential mechanism of QR on MS.