Metabolomic and gut-microbial responses of earthworms exposed to microcystins and nano zero-valent iron in soil.

The earthworm-based vermiremediation facilitated with benign chemicals such as nano zero-valent iron (nZVI) is a promising approach for the remediation of a variety of soil contaminants including cyanotoxins. As the most toxic cyanotoxin, microcystin-LR (MC-LR) enter soil via runoff, irrigated surface water and sewage, and the application of cyanobacterial biofertilizers as part of the sustainable agricultural practice. Earthworms in such remediation systems must sustain the potential risk from both nZVI and MC-LR. In the present study, earthworms (Eisenia fetida) were exposed up to 14 days to MC-LR and nZVI (individually and in mixture), and the toxicity was investigated at both the organismal and metabolic levels, including growth, tissue damage, oxidative stress, metabolic response and gut microbiota. Results showed that co-exposure of MC-LR and nZVI is less potent to earthworms than that of separate exposure. Histological observations in the co-exposure group revealed only minor epidermal brokenness, and KEGG enrichment analysis showed that co-exposure induced earthworms to regulate glutathione biosynthesis for detoxification and reduced adverse effects from MC-LR. The combined use of nZVI promoted the growth and reproduction of soil and earthworm gut bacteria (e.g., Sphingobacterium and Acinetobacter) responsible for the degradation of MC-LR, which might explain the observed antagonism between nZVI and MC-LR in earthworm microcosm. Our study suggests the beneficial use of nZVI to detoxify pollutants in earthworm-based vermiremediation systems where freshwater containing cyanobacterial blooms is frequently used to irrigate soil and supply water for the growth and metabolism of earthworms.

Synthesis of magnetic chitosan-composite biochar and its removal of copper ions (Cu2+) and methylene blue (MB) dye from aqueous solutions.

This study presents the synthesis and evaluation of a magnetic chitosan-modified biochar (M-BC-CS) composite, developed from waste maize straw, for the efficient removal of copper ions (Cu2+) and methylene blue (MB) dye from aqueous solutions. The composite was characterized using advanced techniques such as SEM, BET, FTIR, XPS, and XRD, confirming its enhanced surface area, porosity, and magnetic properties. The study is aimed at investigating the optimal conditions for adsorption of Cu2+ and MB by M-BC-CS through analysis of the influence of diverse adsorbent dosages, pH levels, reaction times, and initial solution concentrations. The findings demonstrated that the equilibrium duration for the adsorption of Cu2+ and MB by M-BC-CS was 60 min, resulting in corresponding equilibrium adsorption quantities of 54.42 mg/g and 67.23 mg/g, respectively. To elucidate the adsorption mechanism, the present investigation applied the pseudo-second-order kinetic model and the Langmuir isotherm. The outcomes suggested that the adsorption process is attributable to single molecular layer chemisorption. XPS and FTIR analysis determined that ion exchange and electrostatic interactions are the predominant mechanisms responsible for the simultaneous adsorption of Cu2+ and MB, and a competitive relationship exists between these mechanisms. In addition, M-BC-CS exhibited exceptional magnetic separation performance, enabling effortless and effective separation when exposed to an external magnetic field. Furthermore, the results demonstrated that M-BC-CS has good reusability and high adsorption capacity also in real wastewater, thus emphasizing its potential as a promising adsorbent for the elimination of Cu2+ and MB from aqueous solutions.

Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids.

Covering: up to June 2024Benzylisoquinoline alkaloids (BIAs) represent a diverse class of plant specialized metabolites derived from L-tyrosine, exhibiting significant pharmacological properties such as anti-microbial, anti-spasmodic, anti-cancer, cardiovascular protection, and analgesic effects. The industrial production of valuable BIAs relies on extraction from plants; however, challenges concerning their low concentration and efficiency hinder drug development. Hence, alternative approaches, including biosynthesis and chemoenzymatic synthesis, have been explored. Model species like Papaver somniferum and Coptis japonica have played a key role in unraveling the biosynthetic pathways of BIAs; however, many aspects, particularly modified steps like oxidation and methylation, remain unclear. Critical enzymes, e.g., CYP450s and methyltransferases, play a substantial role in BIA backbone formation and modification, which is essential for understanding the origin and adaptive evolution of these plant specialized metabolites. This review comprehensively analyzes the structural diversity of reported BIAs and their distribution in plant lineages. In addition, the progress in understanding biosynthesis, evolution, and catalytic mechanisms underlying BIA biosynthesis is summarized. Finally, we discuss the progress and challenges in metabolic engineering, providing valuable insights into BIA drug development and the sustainable utilization of BIA-producing plants.

Raloxifene Prevents Chemically-Induced Ferroptotic Neuronal Death In Vitro and In Vivo.

Ferroptosis, a regulated form of cell death characterized by excessive iron-dependent lipid peroxidation, can be readily induced in cultured cells by chemicals such as erastin and RSL3. Protein disulfide isomerase (PDI) has been identified as an upstream mediator of chemically induced ferroptosis and also a target for ferroptosis protection. In this study, we discovered that raloxifene (RAL), a selective estrogen receptor modulator known for its neuroprotective actions in humans, can effectively inhibit PDI function and provide robust protection against chemically induced ferroptosis in cultured HT22 neuronal cells. Specifically, RAL can bind directly to PDI both in vitro and in intact neuronal cells and inhibit its catalytic activity. Computational modeling analysis reveals that RAL can tightly bind to PDI through forming a hydrogen bond with its His256 residue, and biochemical analysis further shows that when PDI's His256 is mutated to Ala256, RAL loses its inhibition of PDI's catalytic activity. This inhibition of PDI by RAL significantly reduces the dimerization of both the inducible and neuronal nitric oxide synthases and the accumulation of nitric oxide, both of which have recently been shown to play a crucial role in mediating chemically induced ferroptosis through subsequent induction of ROS and lipid-ROS accumulation. In vivo behavioral analysis shows that mice treated with RAL are strongly protected against kainic acid-induced memory deficits and hippocampal neuronal damage. In conclusion, this study demonstrates that RAL is a potent inhibitor of PDI and can effectively prevent chemically induced ferroptosis in hippocampal neurons both in vitro and in vivo. These findings offer a novel estrogen receptor-independent mechanism for RAL's neuroprotective actions in animal models and humans.

Leveraging programmed cell death signature to predict clinical outcome and immunotherapy benefits in postoperative bladder cancer.

Bladder cancer is the fourth most common malignancy in men with poor prognosis. Programmed cell death (PCD) exerts crucial functions in many biological processes and immunotherapy responses of cancers. Cell death signature (CDS) is novel gene signature comprehensively considering the characteristics of 15 patterns of programmed cell death, which could affect the prognosis and immunotherapy benefits of cancer patients. Integrative machine learning procedure including 10 algorithms was conducted to construct a prognostic CDS using TCGA, GSE13507, GSE31684, GSE32984 and GSE48276 datasets. Immunophenoscore, intratumor heterogeneity (ITH), tumor immune dysfunction and exclusion (TIDE) score and five immunotherapy cohorts were used to evaluate the predictive value of CDS in immunotherapy response. The prognostic CDS constructed by StepCox[backward] + Ridge algorithms was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting overall survival of bladder cancer patients with the AUCs at 3-year, 5-year, and 7-year ROC of 0.740, 0.763 and 0.820 in TCGA cohort. Moreover, CDS score acted as an independent risk factor for overall survival rate of bladder cancer patients. Low CDS score had a higher abundance of immuno-activated cells, higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score, lower immune escape score, lower ITH score, lower cancer-related hallmarks score in bladder cancer. The CDS score was higher in non-responders in pan-cancer patients receiving immunotherapy. Our study constructed a novel prognostic CDS, which could serve as an indicator for predicting the prognosis in postoperative bladder cancer cases and immunotherapy benefits in pan-cancer. Low CDS score indicated a better prognosis and immunotherapy benefits.

Screening and stability verification of reference genes in Botrytis cinerea ZX2 fermentation.

Botrytis cinerea, an airborne plant pathogen, holds the potential to synthesize sesquiterpenes, which have been used for the industrial production of abscisic acid. Previously, through our genetic technology, we obtained strain ZX2, whose main product 1´,4´-trans-ABA-diol is physiologically active in plants. In this study, 50 L of fed fermentation was carried out with ZX2 strain to study the stability of expression of TUA, TUB, ATC, EF-1, GAPDH, UCE and GTP genes. Four kinds of software (GeNorm, NormFinder, BestKeeper and Delta Ct) were used to analyze the expression stability of candidate genes, and finally the best reference gene was screened by RefFinder. Based on the results, the ACT was the most stable gene. It was used to normalize the expression levels of two genes related to 1´,4´-trans-ABA-diol production (hmgr and bcaba3) when fed-batch fermentation. Guide the selection of appropriate internal reference genes during the fermentation process to accurately quantify the relative transcription levels of target genes in B.cinerea ZX2.

Advances in the pharmacological mechanisms of berberine in the treatment of fibrosis.

The rising incidence of fibrosis poses a major threat to global public health, and the continuous exploration of natural products for the effective treatment of fibrotic diseases is crucial. Berberine (BBR), an isoquinoline alkaloid, is widely used clinically for its anti-inflammatory, anti-tumor and anti-fibrotic pharmacological effects. Until now, researchers have worked to explore the mechanisms of BBR for the treatment of fibrosis, and multiple studies have found that BBR attenuates fibrosis through different pathways such as TGF-ß/Smad, AMPK, Nrf2, PPAR-γ, NF-κB, and Notch/snail axis. This review describes the anti-fibrotic mechanism of BBR and its derivatives, and the safety evaluation and toxicity studies of BBR. This provides important therapeutic clues and strategies for exploring new drugs for the treatment of fibrosis. Nevertheless, more studies, especially clinical studies, are still needed. We believe that with the continuous implementation of high-quality studies, significant progress will be made in the treatment of fibrosis.

Biofunctionalized dissolvable hydrogel microbeads enable efficient characterization of native protein complexes.

The characterization of protein complex is vital for unraveling biological mechanisms in various life processes. Despite advancements in biophysical tools, the capture of non-covalent complexes and deciphering of their biochemical composition continue to present challenges for low-input samples. Here we introduce SNAP-MS, a Stationary-phase-dissolvable Native Affinity Purification and Mass Spectrometric characterization strategy. It allows for highly efficient purification and characterization from inputs at the pico-mole level. SNAP-MS replaces traditional elution with matrix dissolving during the recovery of captured targets, enabling the use of high-affinity bait-target pairs and eliminates interstitial voids. The purified intact protein complexes are compatible with native MS, which provides structural information including stoichiometry, topology, and distribution of proteoforms, size variants and interaction states. An algorithm utilizes the bait as a charge remover and mass corrector significantly enhances the accuracy of analyzing heterogeneously glycosylated complexes. With a sample-to-data time as brief as 2 hours, SNAP-MS demonstrates considerable versatility in characterizing native complexes from biological samples, including blood samples.

Comparison of reconstruction plates and miniplates in mandibular defect reconstruction with free iliac flap.

OBJECTIVE: Given the increasing demand for precise and reliable reconstructive techniques in maxillofacial surgery, we try to offer valuable insights for clinicians in selecting optimal fixation methods. MATERIALS AND METHODS: Patients were categorized into miniplate and reconstruction plate groups for accuracy and bone healing comparison. We measured gonial angle, intercondylar, intergonial and anterior-posterior distance for general accuracy and distance of segmental endpoint to the sagittal plane for partial accuracy. The bone healing rate of the two groups was compared with CT images at 3, 6 and 12 months after operation. RESULT: Considering directional indicators, the miniplate group exhibited a wider intercondylar distance than the reconstruction plate group (p = 0.029). At 6 months postoperatively, the miniplate group demonstrated a higher bone healing rate compared to the reconstruction plate group, with no significant differences at other time points. CONCLUSION: Over a nearly 5-year review, mandibular reconstruction with vascularized iliac bone flaps showed that reconstruction plates better maintained condylar position accuracy, while miniplates had superior bone healing rates at 6 months. No significant differences were found in other accuracy indices between the two plates. CLINICAL RELEVANCE: Clinicians' selection of fixation plates frequently depends on personal preference rather than evidence-based criteria. This study compares the precision and postoperative osseous healing outcomes of miniplates and reconstruction plates to provide a more scientifically grounded basis for clinical decision-making.

Self-contact snapping metamaterial for tensile energy dissipation.

Mechanical metamaterials for energy dissipation have received significant attention for vibration and impact mitigation. However, existing designs often neglect energy dissipation in the tensile direction, which is crucial for attenuating tensile load and controlling falling descent. Importantly, current energy-dissipating mechanisms including plastic deformation and friction mechanisms, suffer from drawbacks such as reversibility and self-recovery, restricting their effectiveness under tension. To address these limitations, we propose a novel mechanism utilizing self-contact snap-through buckling to develop an energy-dissipating metamaterial. Unlike previous metamaterials, the self-contact snapping metamaterial (SCSM) achieves tensile energy dissipation with fewer unit cells while exhibiting reusability, self-recovery, and low reliance on material selection. A theoretical model is established to explain its energy-dissipating mechanism from the perspective of buckling mode transition. Moreover, the proposed SCSM exhibits sequential snapping behavior and effectively mitigates tensile impacts, as demonstrated through quasi-static and dynamic tests. This work opens new avenues for achieving tensile energy dissipation and inspires future research on energy conversion employing self-contact interactions.

Multi-feature fusion based face forgery detection with local and global characteristics.

The malicious use of deepfake videos seriously affects information security and brings great harm to society. Currently, deepfake videos are mainly generated based on deep learning methods, which are difficult to be recognized by the naked eye, therefore, it is of great significance to study accurate and efficient deepfake video detection techniques. Most of the existing detection methods focus on analyzing the discriminative information in a specific feature domain for classification from a local or global perspective. Such detection methods based on a single type feature have certain limitations in practical applications. In this paper, we propose a deepfake detection method with the ability to comprehensively analyze the forgery face features, which integrates features in the space domain, noise domain, and frequency domain, and uses the Inception Transformer to learn the mix of global and local information dynamically. We evaluate the proposed method on the DFDC, Celeb-DF, and FaceForensic++ benchmark datasets. Extensive experiments verify the effectiveness and good generalization of the proposed method. Compared with the optimal model, the proposed method with a small number of parameters does not use pre-training, distillation, or assembly, but still achieves competitive performance. The ablation experiments evaluate the role of each component.

Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes.

Germline mutations modulate the risk of developing schizophrenia (SCZ). Much less is known about the role of mosaic somatic mutations in the context of SCZ. Deep (239×) whole-genome sequencing (WGS) of brain neurons from 61 SCZ cases and 25 controls postmortem identified mutations occurring during prenatal neurogenesis. SCZ cases showed increased somatic variants in open chromatin, with increased mosaic CpG transversions (CpG>GpG) and T>G mutations at transcription factor binding sites (TFBSs) overlapping open chromatin, a result not seen in controls. Some of these variants alter gene expression, including SCZ risk genes and genes involved in neurodevelopment. Although these mutational processes can reflect a difference in factors indirectly involved in disease, increased somatic mutations at developmental TFBSs could also potentially contribute to SCZ.

Hepatocyte-derived Igκ promotes HCC progression by stabilizing electron transfer flavoprotein subunit α to facilitate fatty acid ß-oxidation.

BACKGROUND: Lipid metabolism dysregulation is a key characteristic of hepatocellular carcinoma (HCC) onset and progression. Elevated expression of immunoglobulin (Ig), especially the Igκ free light chain with a unique Vκ4-1/Jκ3 rearrangement in cancer cells, is linked to increased malignancy and has been implicated in colon cancer tumorigenesis. However, the role of Igκ in HCC carcinogenesis remains unclear. The aim of this study was to elucidate the pivotal roles of hepatocyte-derived Igκ in HCC development. METHODS: The rearrangement sequence and expression level of hepatocyte-derived Igκ in HCC cells were determined via RT-PCR, Sanger sequencing, immunohistochemistry, and western blot analysis. The function of Igκ in HCC tumorigenesis was assessed by silencing Igκ using siRNA or gRNA in various HCC cell lines. To assess the role of Igκ in HCC pathogenesis in vivo, a mouse model with hepatocyte-specific Igκ knockout and diethylnitrosamine (DEN) and carbon tetrachloride (CCL4)-induced HCC was utilized. The molecular mechanism by which Igκ affects HCC tumorigenesis was investigated through multiomics analyses, quantitative real-time PCR, immunoprecipitation, mass spectrometry, immunofluorescence, and metabolite detection. RESULTS: We confirmed that Igκ, especially Vκ4-1/Jκ3-Igκ, is highly expressed in human HCC cells. Igκ depletion inhibited HCC cell proliferation and migration in vitro, and hepatocyte-specific Igκ deficiency ameliorated HCC progression in mice with DEN and CCL4-induced HCC in vivo. Mechanistically, Vκ4-1/Jκ3-Igκ interacts with electron transfer flavoprotein subunit α (ETFA), delaying its protein degradation. Loss of Igκ led to a decrease in the expression of mitochondrial respiratory chain complexes III and IV, resulting in aberrant fatty acid ß-oxidation (FAO) and lipid accumulation, which in turn inhibited HCC cell proliferation and migration. CONCLUSION: Our findings indicate that the Igκ/ETFA axis deregulates fatty acid ß-oxidation, contributing to HCC progression, which suggests that targeting fatty acid metabolism may be an effective HCC treatment strategy. The results of this study suggest that hepatocyte-derived Vκ4-1/Jκ3-Igκ may serve as a promising therapeutic target for HCC.

Comparison of risk factors between lean and non-lean MASLD in individuals with type 2 diabetes: a multicenter study.

OBJECTIVE: A multi-center study in patients with type 2 diabetes mellitus (T2DM) was performed to assess the differences of liver steatosis and fibrosis between lean and non-lean individuals. METHODS: Patients with T2DM from16 centers were recruited and underwent transient elastography examination for diagnosis of liver steatosis and fibrosis. Clinical information including diabetes status, serum lipids profiles, and inflammatory markers were collected. Potential risk factors of liver steatosis and fibrosis in lean (BMI＜23 kg/m2) and non-lean (BMI≥23 kg/m2) groups were analyzed. RESULTS: A total of 1762 patients were included. The prevalence of liver steatosis and fibrosis in lean group were 44.7% and 23.4%. Prevalence of hypertension and cardiovascular disease were higher in lean patients compared to non-lean group. Lean patients with liver steatosis or fibrosis were older, had longer diabetes duration, lower levels of HOMA-IR and serum lipids. Body mass index (BMI), visceral fat area (VFA) and triglyceride were among the most significant correlators of liver steatosis for both non-lean and lean patients. However, lipid profiles were different between two groups. Besides, insulin resistance, BMI and lipid levels were not observed to be associated with fibrosis in lean group. CONCLUSION: Liver steatosis and fibrosis in lean patients with T2DM were less associated with insulin resistance. Risk factors of liver steatosis were different between lean and non-lean patients, indicating the necessity of risk stratification and tailored management strategies.

A monetite/amorphous silica complex for long-term dentine hypersensitivity treatment through the acid stability and mineralization promoting effect of silica.

Dentine hypersensitivity (DH) is often related to the exposure of dentin tubules. Mineral particles, such as hydroxyapatite and bioactive glass, can provide calcium and phosphate ions to temporarily block dentin tubules via the biomineralization process, serving as feasible alternatives for DH treatment. However, due to the acidic microenvironment caused by dietary acids, these particles are easily eroded and dissolved, making it difficult to achieve efficient dentin tubule occlusion. Given the significant stability of silica in dietary acids and its excellent ability to bond with calcium and phosphate ions to form mineralized hydroxyapatite, we proposed to develop a micron-sized monetite/amorphous silica complex (MMSi) hydrosol to effectively seal the exposed dentin tubules. In this study, we hypothesized that the MMSi hydrosol could tolerate acid erosion and concurrently provide active sites for the calcium and phosphate ions to promote biomineralization in comparison to a micron-sized monetite (MM) hydrosol. Hence, the composition and microstructure including the surface morphology, silica content and phase composition of MMSi were investigated to verify the presence of silica. The results of the ion release and in vitro biomineralization process indicated that silica did not hinder the calcium and phosphate ion release and the formation of hydroxyapatite via the biomineralization process. The acid-resistant test suggested that the MMSi hydrosol exhibited a significantly slower corrosion rate than the MM hydrosol when treated with citric acid. Notably, the silica in the MMSi hydrosol retained the ability to induce the nucleation and crystallization of hydroxyapatite during de/remineralization processes. Finally, the MMSi hydrosol was mixed with commercialized toothpaste to explore its efficacy in dentin tubule occlusion via cycling de/remineralization processes. As a result, compared to the MM hydrosol, the toothpaste containing the MMSi hydrosol presented excellent acid-resistant ability and dentin tubule occlusion outcomes, which indicated that the MMSi hydrosol could be a potential promise in the long-term treatment of DH.

Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts.

The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth's magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth's rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.

Effect of different harvest times and processing methods on the vitamin content of Leymus.

Objectives: The objective of this study was to investigate the effect of different harvest times and processing methods on the B vitamins and α-tocopherol contents of Leymus chinensis (Trin.). Methods: L. chinensis was harvested on 11 July (T1 group), 16 July (T2 group), 21 July (T3 group), 26 July (T4 group), and 31 July (T5 group) in 2022 and processed using natural drying and silage fermentation to evaluate fermentation quality, chemical composition, in vitro digestibility and vitamin content. Results: The fermentation quality of L. chinensis silage prepared at all five times of harvest was better. The silage fermentation group showed a significant increase (p < 0.05) in crude protein (CP), thiamin, riboflavin, pyridoxine and α-tocopherol content, a significant decrease (p < 0.05) in water-soluble carbohydrate (WSC) content, and small differences in neutral detergent fibre (NDF), acid detergent fibre (ADF), niacin and pantothenic acid content, when compared to the natural drying group. The content of thiamine, riboflavin, niacin, pantothenic acid and pyridoxine were higher in the pre-harvest period. In silage fermentation, the loss rate of thiamin, riboflavin and pyridoxine was positively correlated with pH and WSC, and the loss rate of thiamin and riboflavin was negatively correlated with lactic acid content. The loss rate of pantothenic acid was negatively correlated with pH and WSC, and positively correlated with lactic acid and ammonia nitrogen. The rate of α-tocopherol synthesis exceeded the rate of catabolism. Conclusion: The content of CP, thiamine, riboflavin, niacin, pantothenic acid and pyridoxine were higher during the early harvest period. Silage fermentation preserved the chemical composition and vitamin content of L. chinensis better than natural drying and had no effect on in vitro digestibility. During silage fermentation, the acidic environment promoted the preservation of thiamin, riboflavin and pyridoxine, but promoted the breakdown of pantothenic acid, α-tocopherol content increased through synthesis.

Advancements and Future Prospects of CRISPR-Cas-Based Population Replacement Strategies in Insect Pest Management.

Population replacement refers to the process by which a wild-type population of insect pests is replaced by a population possessing modified traits or abilities. Effective population replacement necessitates a gene drive system capable of spreading desired genes within natural populations, operating under principles akin to super-Mendelian inheritance. Consequently, releasing a small number of genetically edited insects could potentially achieve population control objectives. Currently, several gene drive approaches are under exploration, including the newly adapted CRISPR-Cas genome editing system. Multiple studies are investigating methods to engineer pests that are incapable of causing crop damage or transmitting vector-borne diseases, with several notable successful examples documented. This review summarizes the recent advancements of the CRISPR-Cas system in the realm of population replacement and provides insights into research methodologies, testing protocols, and implementation strategies for gene drive techniques. The review also discusses emerging trends and prospects for establishing genetic tools in pest management.

Sex-specific Prediction of Cardiogenic Shock After Acute Coronary Syndromes: The SEX-SHOCK Score.

BACKGROUND: and aims: Cardiogenic shock (CS) remains the primary cause of in-hospital death after acute coronary syndromes (ACS), with its plateauing mortality rates approaching 50%. To test novel interventions, personalized risk prediction is essential. The ORBI (Observatoire Régional Breton sur l'Infarctus) score represents the first-of-its-kind risk score to predict in-hospital CS in ACS patients undergoing percutaneous coronary intervention (PCI). However, its sex-specific performance remains unknown, and refined risk prediction strategies are warranted. METHODS: This multinational study included a total of 53 537 ACS patients without CS on admission undergoing PCI. Following sex-specific evaluation of ORBI, regression and machine-learning models were used for variable selection and risk prediction. By combining best-performing models with highest-ranked predictors, SEX-SHOCK was developed, and internally and externally validated. RESULTS: The ORBI score showed lower discriminative performance for the prediction of CS in females than males in Swiss (AUC [95% CI]: 0.78 [0.76-0.81] vs. 0.81 [0.79-0.83]; p=0.048) and French ACS patients (0.77 [0.74-0.81] vs. 0.84 [0.81-0.86]; p=0.002). The newly developed SEX-SHOCK score, now incorporating ST-segment elevation, creatinine, C-reactive protein, and left ventricular ejection fraction, outperformed ORBI in both sexes (females: 0.81 [0.78-0.83]; males: 0.83 [0.82-0.85]; p<0.001), which prevailed following internal and external validation in RICO (females: 0.82 [0.79-0.85]; males: 0.88 [0.86-0.89]; p<0.001) and SPUM-ACS (females: 0.83 [0.77-0.90], p=0.004; males: 0.83 [0.80-0.87], p=0.001). CONCLUSIONS: The ORBI score showed modest sex-specific performance. The novel SEX-SHOCK score provides superior performance in females and males across the entire spectrum of ACS, thus providing a basis for future interventional trials and contemporary ACS management.

Comparison of bloodstream infections due to Corynebacterium striatum, MRSA, and MRSE.

BACKGROUND: Corynebacterium striatum (C. striatum), a common skin and mucosal colonizer, is increasingly considered as an opportunistic pathogen causing bloodstream infections (BSIs). This study aims to investigate the clinical features and outcomes of C. striatum-BSI. METHODS: We included hospitalized cases with C. striatum-positive blood cultures from January 2014 to June 2022 and classified them into C. striatum-BSI group and contamination group; Clinical characteristics, treatments, and outcomes were compared between the C. striatum-BSI group and contamination group, Methicillin-resistant Staphylococcus aureus (MRSA)-BSI and Methicillin-resistant Staphylococcus epidermidis (MRSE)-BSI. RESULTS: Fifty-three patients with positive C. striatum blood cultures were identified. Among them, 25 patients were classified as C. striatum-BSI, with 21 as contamination cases. And 62 cases of MRSA-BSI and 44 cases of MRSE-BSI were identified. Compared to the contaminated group, the C. striatum-BSI group had a shorter time to positivity of blood cultures (27.0 h vs. 42.5 h, P = 0.011). C. striatum-BSI group had a longer time to positivity (27 h) when compared to both the MRSA (20 h) and MRSE groups (19 h) (p < 0.05). Appropriate therapy within 24 h of BSI onset was significantly lower in the C. striatum group (28%) compared to the MRSA (64.5%) and MRSE (65.9%) groups (p < 0.005). The 28-day mortality was higher in the C. striatum group (52.0%) compared to the MRSA (25.8%) and MRSE (18.2%) groups.  CONCLUSIONS: Given the distinct characteristics of C. striatum-BSI, including a longer time to positivity than other Gram-positive bacteria and higher mortality rates, we suggest prescribing early appropriate antibiotics if C. striatum-BSI is suspected.