Androgen Receptor Mediates Dopamine Agonist Resistance by Regulating Intracellular reactive oxygen species (ROS) in Prolactin-secreting Pituitary Adenoma.

AIMS: Dopamine agonists (DA) are the first-line treatment for patients with prolactin-secreting pituitary adenoma (PRL adenoma). However, a subset of individuals exhibits poor responses, known as DA resistance. Previous studies have reported that DA resistance is more prevalent in male patients. This study aims to investigate the relationship between androgen receptor (AR) expression and DA resistance, as well as to explore underlying mechanisms of AR-mediated DA resistance. RESULTS: Our results demonstrated that patients with higher AR expression exhibit greater resistance to DA in our cohort of DA-resistant PRL adenoma. Furthermore, AR was found to be involved in cell proliferation, PRL secretion, and resistance to BRC both in vitro and in vivo. Mechanistically, we demonstrated that intracellular ROS function as upstream mediators of apoptosis and ferroptosis following BRC treatment. As a ligand-dependent transcription factor, AR could translocate to the nucleus and transcriptionally promote NRF2 expression, which regulates intracellular ROS levels, thereby enhancing cell viability, and conferring DA resistance to PA cells. Finally, AR targeting agents were used to inhibit AR signaling, downregulate NRF2 transcription, and sensitize PA cells to BRC treatment. Conclusion and innovation: We demonstrated that AR plays a crucial role in mediating DA resistance in PRL-adenoma. Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas.

Examining the Relationship Between Social Support, Self-Efficacy, Diabetes Self-Management, and Quality of Life Among Rural Individuals With Type 2 Diabetes in Eastern China: Path Analytical Approach.

BACKGROUND: Patients with type 2 diabetes (T2D) in rural China frequently exhibit inadequate diabetes self-management (DSM) and a reduced quality of life (QoL). Social support and self-efficacy are known to influence DSM and QoL. However, the pathways through which social support and self-efficacy impact DSM and QoL among patients with T2D in rural China has yet to be fully elucidated. OBJECTIVE: This study offers a foundation for developing policies in rural chronic disease management, thereby, contributing to the improvement of T2D prevention and control in China and other transitional countries. METHODS: This study used a cross-sectional design, collecting data from a survey conducted between May and July 2021 on DSM and QoL among rural patients diagnosed with T2D in 2 townships in East China. All patients with T2D were enrolled through cluster sampling from the township health center database, and a questionnaire survey was administered by investigators. Structural equation modeling and multiple regression analyses were used to explore the pathways through which social support influences DSM and QoL, as well as the mediating role of self-efficacy. RESULTS: It was found that the DSM score (mean 37.42, SD 7.70) was less than half of the maximum theoretical score. The QoL score (mean 48.92, SD 8.88) accounted for 36% of the maximum theoretical score. Social support directly and positively affected the DSM and QoL of Chinese rural patients with T2D (P<.01); an increase of 1 unit in social support was associated with a direct increment of 0.339 units in DSM and 0.397 units in QoL. Self-efficacy played a positive mediating role (P<.01), further increasing DSM and QoL by 0.147 and 0.159 units, respectively. The mediating effect of self-efficacy accounted for 30.2% and 28.6% of the total effect of social support on DSM and QoL. Furthermore, the family and friend dimension of social support, along with the symptom and disease management dimensions of self-efficacy, were significantly associated with DSM or QoL (P<.01). CONCLUSIONS: The study confirmed the direct and indirect influences of social support on DSM and QoL and elucidated the mediating effect of self-efficacy among rural patients with T2D in eastern China. Interventions should be developed to enhance both social support and self-efficacy, creating a positive cycle of mutual reinforcement to improve DSM and QoL among this group.

Inhibition of heme-thiolate monooxygenase CYP1B1 prevents hepatic stellate cell activation and liver fibrosis by accumulating trehalose.

Activation of extracellular matrix-producing hepatic stellate cells (HSCs) is a key event in liver fibrogenesis. We showed that the expression of the heme-thiolate monooxygenase cytochrome P450 1B1 (CYP1B1) was elevated in human and mouse fibrotic livers and activated HSCs. Systemic or HSC-specific ablation and pharmacological inhibition of CYP1B1 attenuated HSC activation and protected male but not female mice from thioacetamide (TAA)-, carbon tetrachloride (CCl4)-, or bile duct ligation (BDL)-induced liver fibrosis. Metabolomic analysis revealed an increase in the disaccharide trehalose in CYP1B1-deficient HSCs resulting from intestinal suppression of the trehalose-metabolizing enzyme trehalase, whose gene we found to be a target of RARα. Trehalose or its hydrolysis-resistant derivative lactotrehalose exhibited potent antifibrotic activity in vitro and in vivo by functioning as an HSC-specific autophagy inhibitor, which may account for the antifibrotic effect of CYP1B1 inhibition. Our study thus reveals an endobiotic function of CYP1B1 in liver fibrosis in males, mediated by liver-intestine cross-talk and trehalose. At the translational level, pharmacological inhibition of CYP1B1 or the use of trehalose/lactotrehalose may represent therapeutic strategies for liver fibrosis.

Association between widowhood and cognitive function among Chinese older adults with hearing impairment: the moderating effect of social support and participation.

BACKGROUND: Older adults with hearing impairments are vulnerable to cognitive impairment. Although previous reports suggest a correlation between widowhood and cognitive impairment, further investigation is needed to elucidate the effect of widowhood on cognitive function and the moderating effects of social support and participation on widowhood-related cognitive impairment in this vulnerable demographic. METHODS: The study's data were sourced from the nationally representative Chinese Longitudinal Healthy Longevity Survey (CLHLS) for the years 2011, 2014, and 2018. Multiple linear regression was used to analyze the association between widowhood and cognitive function among older adults. Multivariate logistic regression examined the effect of widowhood on the likelihood of experiencing various levels of cognitive impairment in older adults with hearing impairments. A moderating effect model explored the roles of social support and participation in mitigating widowhood-related cognitive impairment. RESULTS: The cognitive function of older adults with hearing impairment was found to be lower than that of those without hearing impairment. Widowhood was significantly negatively correlated with Mini-Mental State Examination (MMSE) scores in older adults, both with (Coef. = -0.898) and without (Coef.: = -0.680) hearing impairments. A stronger association was observed between widowhood and declining cognitive function among older adults with hearing impairment. Specifically, widowhood may be more likely to significantly increase the likelihood of moderate and severe cognitive impairment (RRR = 1.326, 1.538) among older adults with hearing impairments. Social support and social participation significantly moderated the cognitive impairment associated with widowhood among hearing-impaired older adults. These forms of support and engagement are buffers against the risk of widowhood-related cognitive impairment among this demographic. CONCLUSIONS: Our findings indicate that widowhood is significantly associated with cognitive impairment in older adults with hearing impairment. Social support and participation help mitigate this risk. Strategies should prioritize early screening, specialized cognitive rehabilitation, comprehensive care, and enhancing social support and participation to maintain cognitive health in this vulnerable population following widowhood.

miR-451-targeted PSMB8 promotes PRRSV infection by degrading IRF3.

Porcine respiratory and reproductive syndrome (PRRS) is one of the most devastating infectious diseases of pigs, causing reproductive failures in sows and severe respiratory symptoms in piglets and growing pigs. MicroRNAs (miRNAs) are reported to play an essential role in virus-host interactions. In this study, we demonstrated that miR-451 enhanced type I interferon (IFN-I) production through targeting proteasome subunit ß8 (PSMB8), therefore restricting PRRS virus (PRRSV) replication. We showed that the expression of PSMB8 was upregulated by PRRSV infection, and knockdown of PSMB8 inhibited PRRSV replication by promoting IFN-I production. Moreover, we demonstrated that PSMB8 interacted with the regulatory domain of IRF3 to mediate K48-linked polyubiquitination and degradation of IRF3. Also, importantly, we showed that PSMB8, as a target gene of miR-451, negatively regulated IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to modulate innate immune responses. IMPORTANCE: Porcine respiratory and reproductive syndrome virus (PRRSV), as a huge threat to the swine industry, is a causative agent that urgently needs to be solved. The dissecting of PRRSV pathogenesis and understanding of the host-pathogen interaction will provide insights into developing effective anti-PRRSV strategies. In this study, we showed that miR-451 dramatically inhibited PRRSV replication by targeting proteasome subunit ß8 (PSMB8), a subunit of the immunoproteasome. Mutation of PSMB8 is often related to autoinflammatory diseases due to the elevated IFN production. We revealed that PSMB8 downregulated IFN production by promoting IRF3 degradation. In addition, we showed that PRRSV infection upregulated PSMB8 expression. Taken together, our findings reveal that miR-451 is a negative regulator of PRRSV replication, and PSMB8, a target gene of miR-451, negatively regulates IFN-I production by promoting IRF3 degradation, which is a previously unknown mechanism for PSMB8 to regulate innate immune responses.

Zero-shot prediction of mutation effects with multimodal deep representation learning guides protein engineering.

Mutations in amino acid sequences can provoke changes in protein function. Accurate and unsupervised prediction of mutation effects is critical in biotechnology and biomedicine, but remains a fundamental challenge. To resolve this challenge, here we present Protein Mutational Effect Predictor (ProMEP), a general and multiple sequence alignment-free method that enables zero-shot prediction of mutation effects. A multimodal deep representation learning model embedded in ProMEP was developed to comprehensively learn both sequence and structure contexts from ~160 million proteins. ProMEP achieves state-of-the-art performance in mutational effect prediction and accomplishes a tremendous improvement in speed, enabling efficient and intelligent protein engineering. Specifically, ProMEP accurately forecasts mutational consequences on the gene-editing enzymes TnpB and TadA, and successfully guides the development of high-performance gene-editing tools with their engineered variants. The gene-editing efficiency of a 5-site mutant of TnpB reaches up to 74.04% (vs 24.66% for the wild type); and the base editing tool developed on the basis of a TadA 15-site mutant (in addition to the A106V/D108N double mutation that renders deoxyadenosine deaminase activity to TadA) exhibits an A-to-G conversion frequency of up to 77.27% (vs 69.80% for ABE8e, a previous TadA-based adenine base editor) with significantly reduced bystander and off-target effects compared to ABE8e. ProMEP not only showcases superior performance in predicting mutational effects on proteins but also demonstrates a great capability to guide protein engineering. Therefore, ProMEP enables efficient exploration of the gigantic protein space and facilitates practical design of proteins, thereby advancing studies in biomedicine and synthetic biology.

Does Two-Step Infusion Improve the Pharmacokinetics/Pharmacodynamics Target Attainment of Meropenem in Critically Ill Patients?

The optimal method for administering meropenem remains controversial. This study was conducted to explore the optimal two-step infusion strategy (TIT), and to investigate whether TIT is superior to intermittent infusion therapy (IIT) and prolonged infusion therapy (PIT). A physiologically based pharmacokinetics model for critically ill patients was established and evaluated. The validated model was utilized to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) target attainment of meropenem. The PK/PD target attainment of different TITs varied greatly, and the total infusion duration and the first-step dose greatly affected these values. The optimal TIT was 0.25 g (30 min) + 0.75 g (150 min) at MICs of ≤2 mg/L, and 0.25 g (45 min) + 0.75 g (255 min) at MICs of 4-8 mg/L. The PK/PD target attainment of optimal TIT, PIT, and IIT were 100 % at MICs of ≤1 mg/L. When MIC increased to 2-8 mg/L, the PK/PD target attainment of optimal TIT was similar to that of PIT and higher than IIT. In conclusion, TIT did not significantly improve the PK/PD target attainment of meropenem compared with PIT. IIT is adequate at MICs of ≤1 mg/L, and PIT may be the optimal meropenem infusion method in critically ill patients with MICs of 2-8 mg/L.

Process-Informed Subsampling Improves Subseasonal Rainfall Forecasts in Central America.

Subseasonal rainfall forecast skill is critical to support preparedness for hydrometeorological extremes. We assess how a process-informed evaluation, which subsamples forecasting model members based on their ability to represent potential predictors of rainfall, can improve monthly rainfall forecasts within Central America in the following month, using Costa Rica and Guatemala as test cases. We generate a constrained ensemble mean by subsampling 130 members from five dynamic forecasting models in the C3S multimodel ensemble based on their representation of both (a) zonal wind direction and (b) Pacific and Atlantic sea surface temperatures (SSTs), at the time of initialization. Our results show in multiple months and locations increased mean squared error skill by 0.4 and improved detection rates of rainfall extremes. This method is transferrable to other regions driven by slowly-changing processes. Process-informed subsampling is successful because it identifies members that fail to represent the entire rainfall distribution when wind/SST error increases.

Predicting pre- and post-operative acute kidney injury in elderly patients with coronary artery disease.

Background: Limited evidence exists regarding the clinical baseline characteristics at admission for acute kidney injury (AKI) before and after interventional cardiac procedures (ICP) in elderly patients with coronary artery disease (CAD). Methods: A total of 488 elderly patients were enrolled in this retrospective single-center study conducted from January 2019 to July 2022, and a classification and regression tree (CART) analysis was performed to identify the high-risk population. Results: The AKI incidence was 21.1 % (103/488) in this study, with 27 and 76 individuals developing AKI before and after ICP, respectively. CART analysis revealed that exposure to nephrotoxic drugs and diuretics had the strongest predictive capacities for identifying patients at risk of developing pre-ICP AKI, with the incidence among these high-risk patients ranging from 6.5 % to 13.8 %. Meanwhile, the optimum discriminators for identifying those at high risk of post-ICP AKI were the administration of diuretics, D-value ≤ -860 mL, age >73 years, and administration of nephrotoxic drugs, and the latter model predicted that the AKI incidence among high-risk patients was between 50.0 % and 60.0 %. Conclusions: Elderly patients with CAD exhibited an elevated incidence of AKI. CART models suggested that exposure to nephrotoxic drugs and diuretics, D-value, and age were significantly associated with AKI in the elderly with CAD. Importantly, these baseline characteristics at admission could be utilized to identify elderly patients at high risk of pre- and post-ICP AKI.

Association between dysphagia and activities of daily living in older adults: a systematic review and meta-analysis.

PURPOSE: Numerous epidemiological studies have suggested a possible association between dysphagia and the risk of decline in Activities of daily living (ADL) among older adults. This systematic review and meta-analysis aimed to elucidate the relationship between dysphagia and ADL in older adults. METHODS: PubMed, Web of Science, Cochrane Library, Embase, Ebsco, MEDLINE, Wiley, CINAHL, and Ovid databases were comprehensively examined for relevant studies published up to October 31, 2022. Quantitative studies published in English were included to explore the relationship between dysphagia and ADL in people aged 65 years and older. The NIH Quality Assessment Tool was used to assess the study quality. R software was used to draw forest plots and I2 was employed to indicate study heterogeneity. Sensitivity analysis was performed using the one-by-one exclusion method. Publication bias was measured using funnel plots and Egger's test. RESULTS: A total of 3,498 studies were retrieved from the database, 22 of which were eventually included in the systematic evaluation, and 14 of which were subjected to meta-analysis. Data from nine studies were categorical variables, and meta-analysis results showed that swallowing disorders in older adults were associated with a lower ability to perform ADL (OR = 3.39, 95% CI: 2.55-4.50, p < 0.001), with moderate heterogeneity (I2 = 62%, p = 0.006). Data from seven studies were continuous variables, resulting in a negative association between the prevalence of dysphagia and ADLs in older adults (SMD = -0.80, 95% CI: -1.08 to -0.51, p < 0.001), with high heterogeneity (I2 = 94%, p < 0.001). Sensitivity analysis showed robust results, funnel plots and Egger's test indicated no publication bias. CONCLUSION: Dysphagia is significantly associated with the capacity to perform ADL. Prevention and screening of dysphagia in older patients dependent on others for daily care are needed. Further long-term studies are needed in the future to prove causality.

Chitosan-based GOx@Co-MOF composite hydrogel: A promising strategy for enhanced antibacterial and wound healing effects.

A novel composite hydrogel was synthesized via Schiff base reaction between chitosan and di-functional poly(ethylene glycol) (DF-PEG), incorporating glucose oxidase (GOx) and cobalt metal-organic frameworks (Co-MOF). The resulting CS/PEG/GOx@Co-MOF composite hydrogel was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and energy-dispersive X-ray spectroscopy (EDS). The results confirmed successful integration and uniform distribution of Co-MOF within the hydrogel matrix. Functionally, the hydrogel exploits the catalytic decomposition of glucose by GOx to generate gluconic acid and hydrogen peroxide (H2O2), while Co-MOF gradually releases metal ions and protects GOx. This synergy enhanced the antibacterial activity of the composite hydrogel against both Gram-positive (S. aureus) and Gram-negative bacteria (E. coli), outperforming conventional chitosan-based hydrogels. The potential of the composite hydrogel in treating wound infections was evaluated through antibacterial and wound healing experiments. Overall, CS/PEG/GOx@Co-MOF hydrogel holds great promise for the treatment of wound infections, paving the way for further research and potential clinical applications.

Methyl-CpG-binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor.

Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.

Applying Resistant Starch to Improve the Gel and Water Retention of Reduced-Fat Pork Batter.

Emulsified meat products contain high animal fat content, and excessive intake of animal fat is not good for health, so people are paying more and more attention to reduced-fat meat products. This study investigated the impact of varying proportions of pork back-fat and/or resistant starch on the proximate composition, water and fat retention, texture properties, color, and rheology characteristic of pork batter. The results found that replacing pork back-fat with resistant starch and ice water significantly decreased the total lipid and energy contents of cooked pork batter (p < 0.05) while improving emulsion stability, cooking yield, texture, and rheology properties. Additionally, when the pork back-fat replacement ratio was no more than 50%, there was a significant increase in emulsion stability, cooking yield, hardiness, springiness, cohesiveness, chewiness, and L* and G' values (p < 0.05). Furthermore, resistant starch and ice water enhanced myosin head and tail thermal stability and increased G' value at 80 °C. However, the initial relaxation times significantly decreased (p < 0.05) and the peak ratio of P21 significantly increased from 84.62% to 94.03%, suggesting reduced fluidity of water. In conclusion, it is feasible to use resistant starch and ice water as a substitute for pork back-fat in order to produce reduced-fat pork batter with favorable gel and rheology properties.

Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.

Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in microbiome composition are associated with disease pathology. Stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes in the context of stress. Using a model of chronic stress, we show that the glycocalyx protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction of Muc13 is mediated by the Hnf4 transcription factor family. Finally, we determine that deleting Muc13 is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a novel regulator of mucin 13 expression.

Predictive analytics for cardiovascular patient readmission and mortality: An explainable approach.

BACKGROUND: Cardiovascular patients experience high rates of adverse outcomes following discharge from hospital, which may be preventable through early identification and targeted action. This study aimed to investigate the effectiveness and explainability of machine learning algorithms in predicting unplanned readmission and death in cardiovascular patients at 30 days and 180 days from discharge. METHODS: Gradient boosting machines were trained and evaluated using data from hospital electronic medical records linked to hospital administrative and mortality data for 39,255 patients admitted to four hospitals in New South Wales, Australia between 2017 and 2021. Sociodemographic variables, admission history, and clinical information were used as potential predictors. The performance was compared to LASSO regression, as well as the HOSPITAL and LACE risk score indices. Important risk factors identified by the gradient-boosting machine model were explored using Shapley values. RESULTS: The models performed well, especially for the mortality outcomes. Area under the receiver operating characteristic curve values were 0.70 for readmission and 0.87-0.90 for mortality using the full gradient boosting machine algorithms. Among the top predictors for 30-day and 180-day readmission were increased red cell distribution width, old age (especially above 80 years), high measured troponin and urea levels, not being married or in a relationship, and low albumin levels. For mortality, these included increased red cell distribution width, old age (especially older than 70 years), high measured troponin and urea levels, high neutrophil and monocyte counts, and low eosinophil and lymphocyte counts. The Shapley values gave clear insight into the dynamics of decision-tree-based models. CONCLUSIONS: We demonstrated an explainable predictive algorithm to identify cardiovascular patients who are at high risk of readmission or death at discharge from the hospital and identified key risk factors.

Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer.

Chemo-immunotherapy combinations have been regarded as one of the most practical ways to improve immunotherapy response in cancer patients. In this study, we integrate the transcriptomics data from anti-PD-1-treated tumors and compound-treated cancer cell lines to systematically screen for chemo-immunotherapy synergisms in silico. Through analyzing anti-PD-1 induced expression changes in patient tumors, we develop a shift ability score to measure if a chemotherapy or a small molecule inhibitor treatment can shift anti-PD-1 resistance in tumor cells. By applying shift ability analysis to 41,321 compounds and 16,853 shRNA treated cancer cell lines transcriptomic data, we characterize the landscape of chemo-immunotherapy synergism and experimentally validated a mitochondrial RNA-dependent mechanism for drug-induced immune activation in tumor. Our study represents an effort to mechanistically characterize chemo-immunotherapy synergism and will facilitate future pre-clinical and clinical studies.

A General Concept for the Electronic and Steric Modification of 1-Metallacyclobuta-2,3-dienes: A Case Study of Group 4 Metallocene Complexes.

The synthesis of group 4 metal 1-metallacyclobuta-2,3-dienes as organometallic analogues of elusive 1,2-cyclobutadiene has so far been limited to SiMe3 substituted examples. We present the synthesis of two Ph substituted dilithiated ligand precursors for the preparation of four new 1-metallacyclobuta-2,3-dienes [rac-(ebthi)M] (M=Ti, Zr; ebthi=1,2-ethylene-1,10-bis(η5-tetrahydroindenyl)). The organolithium compounds [Li2(RC3Ph)] (1 b: R=Ph, 1 c: R=SiMe3) as well as the metallacycles of the general formula [rac-(ebthi)M(R1C3R2)] (2 b: M=Ti, R1=R2=Ph, 2 c: M=Ti, R1=Ph, R2=SiMe3; 3 b: M=Zr, R1=R2=Ph; 3 c: M=Zr, R1=Ph, R2=SiMe3) were fully characterised. Single crystal X-ray diffraction and quantum chemical bond analysis of the Ti and Zr complexes reveal ligand influence on the biradicaloid character of the titanocene complexes. X-band EPR spectroscopy of structurally similar Ti complexes [rac-(ebthi)Ti(Me3SiC3SiMe3)] (2 a), 2 b, and 2 c was carried out to evaluate the accessibility of an EPR active triplet state. Cyclic voltammetry shows that introduction of Ph groups renders the complexes easier to reduce. 13C CPMAS NMR analysis provides insights into the cause of the low field shift of the resonances of metal-bonded carbon atoms and provides evidence of the absence of the ß-C-Ti interaction.

Global Patterns of Agricultural Machine and Equipment Injuries- A Systematic Literature Review.

OBJECTIVES: Agriculture is the one of the hazardous industries in the world. Though there is significant investment in agricultural safety, machine injuries continue to be the leading cause of agriculture injuries worldwide. The objective of this study was to provide a comprehensive literature review on global patterns in agricultural machine injuries and establish a framework for future research aimed at addressing safety concerns in the agriculture sector. METHODS: The existing scholarship on farm machine injuries can be categorized into three main areas: a) farming machine/equipment injuries, b) factors associated with these injuries, and c) injury patterns. RESULTS: Overall, the findings highlight that farm tractors are the primary source of injuries for both fatal and non-fatal incidents regardless of region. Other common sources of injuries were harvesting machinery and hand/power tools in Asia, ATVs in North America and woodworking machinery in Europe. Inadequate training in operating farm equipment was reported as the most likely factor contributing to machine-related injuries. Lastly, the patterns of injuries vary based on the interaction between humans and machinery. For instance, rollovers often result in severe head and fracture injuries, while thresher incidents can lead to amputation of hands, arms, and other body parts. CONCLUSION: Addressing these injuries by implementing safety protocols will not only enhance the well-being of farm workers but potentially attract more workers to the sector, which is currently experiencing labor shortages due to machine-related injuries.

A high-performance photoelectrochemical sensor based on CdS-Au composite nanomaterials and localized surface plasmon resonance for ultrasensitive detection of ascorbic acid.

Ascorbic acid (AA), which plays a vital role in the metabolism of the human body, is closely correlated with various diseases, including rheumatoid arthritis, scurvy, Parkinson's disease, urinary stones, and diarrhea. The detection of AA is of great significance for early prevention and diagnosis of related diseases. In this paper, a high-performance photoelectrochemical (PEC) sensor was constructed based on cadmium sulfide-gold (CdS-Au) composite nanomaterials for ultrasensitive ascorbic acid (AA) detection. Due to the localized surface plasmon resonance (LSPR) effect of gold nanoparticles (AuNPs), the PEC performance of CdS-Au composite nanomaterials was significantly improved compared to CdS semiconductor nanomaterials. Under the optimal conditions, the AA concentration was linearly related to the photocurrent signal in the range of 0.01 µM-200 µM, with the detection limit being 0.2 nM (S/N = 3) and the sensitivity being 642.9 µA mM-1 cm-2. In addition, the mechanism of the PEC sensor based on CdS-Au composite nanomaterials for ultrasensitive AA detection was discussed. Lastly, the self-constructed PEC sensors have been successfully applied in detecting AA in vitamin C tablets and actual blood samples, meeting the detection criteria required by the Chinese Pharmacopoeia (CP, 2020 edition). The self-fabricated PEC sensors in this paper are expected to be used for quality assessment of AA-related drugs and diagnosis of relevant diseases.

Agricultural Injury Surveillance in the United States and Canada: A Systematic Literature Review.

INTRODUCTION: Agricultural injuries remain a major concern in North America, with a fatal injury rate of 19.5 deaths per 100,000 workers in the United States. Numerous research efforts have sought to compile and analyze records of agricultural-related injuries and fatalities at a national level, utilizing resources, ranging from newspaper clippings and hospital records to Emergency Medical System (EMS) data, death certifications, surveys, and other multiple sources. Despite these extensive efforts, a comprehensive understanding of injury trends over extended time periods and across diverse types of data sources remains elusive, primarily due to the duration of data collection and the focus on specific subsets. METHODS: This systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, consolidates and analyzes agricultural injury surveillance data from 48 eligible papers published between 1985 and 2022 to offer a holistic understanding of trends and challenges. RESULTS: These papers, reporting an average of 25,000 injuries each, were analyzed by database source type, injury severity, nature of injury, body part, source of injury, event/exposure, and age. One key finding is that the top source of injury or event/exposure depends on the chosen surveillance system and injury severity, underscoring the need of diverse data sources for a nuanced understanding of agricultural injuries. CONCLUSION: This study provides policymakers, researchers, and practitioners with crucial insights to bolster the development and analysis of surveillance systems in agricultural safety. The overarching aim is to address the pressing issue of agricultural injuries, contributing to a safer work environment and ultimately enhancing the overall well-being of individuals engaged in agriculture.