Universal Fragility of Spin Glass Ground States under Single Bond Changes.

We consider the effect of perturbing a single bond on ground states of nearest-neighbor Ising spin glasses, with a Gaussian distribution of the coupling constants, across various two- and three-dimensional lattices and regular random graphs. Our results reveal that the ground states are strikingly fragile with respect to such changes. Altering the strength of only a single bond beyond a critical threshold value leads to a new ground state that differs from the original one by a droplet of flipped spins whose boundary and volume diverge with the system size-an effect that is reminiscent of the more familiar phenomenon of disorder chaos. These elementary fractal-boundary zero-energy droplets and their composites feature robust characteristics and provide the lowest-energy macroscopic spin-glass excitations. Remarkably, within numerical accuracy, the size of such droplets conforms to a universal power-law distribution with exponents that depend on the spatial dimension of the system. Furthermore, the critical coupling strengths adhere to a stretched exponential distribution that is predominantly determined by the local coordination number.

Modeling multi-component separation in hydrophobic interaction chromatography with improved parameter-by-parameter estimation method.

Mechanistic models are powerful tools for chromatographic process development and optimization. However, hydrophobic interaction chromatography (HIC) mechanistic models lack an effective and logical parameter estimation method, especially for multi-component system. In this study, a parameter-by-parameter method for multi-component system (called as mPbP-HIC) was derived based on the retention mechanism to estimate the six parameters of the Mollerup isotherm for HIC. The linear parameters (ks,i and keq,i) and nonlinear parameters (ni and qmax,i) of the isotherm can be estimated by the linear regression (LR) and the linear approximation (LA) steps, respectively. The remaining two parameters (kp,i and kkin,i) are obtained by the inverse method (IM). The proposed method was verified with a two-component model system. The results showed that the model could accurately predict the protein elution at a loading of 10 g/L. However, the elution curve fitting was unsatisfactory for high loadings (12 g/L and 14 g/L), which is mainly attributed to the demanding experimental conditions of the LA step and the potential large estimation error of the parameter qmax. Therefore, the inverse method was introduced to further calibrate the parameter qmax, thereby reducing the estimation error and improving the curve fitting. Moreover, the simplified linear approximation (SLA) was proposed by reasonable assumption, which provides the initial guess of qmax without solving any complex matrix and avoids the problem of matrix unsolvable. In the improved mPbP-HIC method, qmax would be initialized by the SLA and finally determined by the inverse method, and this strategy was named as SLA+IM. The experimental validation showed that the improved mPbP-HIC method has a better curve fitting, and the use of SLA+IM reduces the error accumulation effect. In process optimization, the parameters estimated by the improved mPbP-HIC method provided the model with excellent predictive ability and reasonable extrapolation. In conclusion, the SLA+IM strategy makes the improved mPbP-HIC method more rational and can be easily applied to the practical separation of protein mixture, which would accelerate the process development for HIC in downstream of biopharmaceuticals.

A highly stable full-polymer electrochemical deionization system: dopant engineering & mechanism study.

Electrochemical deionization (ECDI) has emerged as a promising technology for water treatment, with faradaic ECDI systems garnering significant attention due to their enhanced performance potential. This study focuses on the development of a highly stable and efficient, full-polymer (polypyrrole, PPy) ECDI system based on two key strategies. Firstly, dopant engineering, involving the design of dopants with a high charge/molecular weight (MW) ratio and structural complexity, facilitating their effective integration into the polymer backbone. This ensures sustained contribution of strong negative charges, enhancing system performance, while the bulky dopant structure promotes stability during extended operation cycles. Secondly, operating the system with well-balanced charges between deionization and concentration processes significantly reduces irreversible reactions on the polymer, thereby mitigating dopant leakage. Implementing these strategies, the PPy(PSS)//PPy(ClO4) (PSS: polystyrene sulfonate) system achieves a high salt removal capacity (SRC) of 48 mg g-1, an ultra-low energy consumption (EC) of 0.167 kW h kgNaCl-1, and remarkable stability, with 96% SRC retention after 104 cycles of operation. Additionally, this study provides a detailed degradation mechanism based on pre- and post-cycling analyses, offering valuable insights for the construction of highly stable ECDI systems with superior performance in water treatment applications.

Effectiveness and safety of continuous low-molecular-weight heparin versus switching to direct oral anticoagulants in cancer-associated venous thrombosis.

Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35-0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61-0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83-1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Preoperative electroacupuncture versus sham electroacupuncture for the treatment of postoperative ileus after laparoscopic surgery for colorectal cancer in China: a study protocol for a multicentre, randomised, sham-controlled trial.

INTRODUCTION: Postoperative ileus (POI) is a postoperative complication that can cause lingering recovery after colorectal resection and a heavy healthcare system burden. Acupuncture aims to prevent postoperative complications, reduce the duration of POI, help recovery and shorten hospital stays. We hypothesise that preoperative electroacupuncture (EA) can promote POI recovery under the enhanced recovery after surgery protocol after laparoscopic surgery in patients with POI. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 80 patients will be enrolled and randomly assigned to the EA or sham electroacupuncture (SA) group. The eligible patients will receive EA or SA for one session per day with treatment frequency starting on preoperative day 1 for four consecutive days. The primary outcome is the time to first defecation. The secondary outcomes include the time to first flatus, length of postoperative hospital stay, time to tolerability of semiliquid and solid food, postoperative nausea, vomiting, pain and extent of abdominal distention, time to first ambulation, preoperative anxiety, 30-day readmission rate, the usage of anaesthetics and analgesics during operation, length of postanaesthesia care unit stay. A mechanistic study by single-cell RNA sequencing in which postintervention normal intestinal tissue samples will be collected. The results of this study will provide evidence of the effects of acupuncture on POI and promote good clinical decision to millions of patients globally every year. ETHICS AND DISSEMINATION: This study has been approved by the ethical application of Beijing University of Chinese Medicine (2022BZYLL0401), Beijing Friendship Hospital Affiliated to Capital Medical University(2022-P2-368-02), Cancer Hospital Chinese Academy of Medical Science (23/175-3917), Huanxing Cancer Hospital (2023-002-02). The results will be published in a medical journal. In addition, we plan to present them at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077633.

Viola yedoensis Makino alleviates lipopolysaccharide-induced intestinal oxidative stress and inflammatory response by regulating the gut microbiota and NF-κB-NLRP3/ Nrf2-MAPK signaling pathway in broiler.

Viola yedoensis Makino (Vy) is a well-known traditional Chinese medicine widely used to treat inflammatory diseases. However, the regulatory effects of dietary Vy supplementation on lipopolysaccharide (LPS)-induced intestinal damage in broilers and the underlying molecular mechanisms remain unclear. In this study, broilers were intraperitoneally injected with 1 mg/kg LPS on days 17, 19 and 21 to induce intestinal damage. Vy supplementation at 0.5, 1.5 and 4.5 % in the diet was administered separately for 21 days to investigate the potential protective effects of Vy supplementation against LPS-induced intestinal impairment in broilers. Vy supplementation improved intestinal morphology and restored growth performance. Vy supplementation attenuated intestinal inflammation by regulating the nuclear factor kappa B (NF-κB) / NLR family pyrin domain-containing 3 (NLRP3) signaling pathway and inhibited its downstream pro-inflammatory factor levels. In addition, Vy supplementation relieved intestinal oxidative impairment by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) / mitogen-activated protein kinase (MAPK) signaling pathway and downstream antioxidant enzyme activity. Vy supplementation reduced LPS-induced mitochondrial damage and apoptosis. Furthermore, Vy supplementation alleviated LPS-induced intestinal inflammation and oxidative damage in chickens by increasing the abundance of protective bacteria (Lactobacillus and Romboutsia) and reducing the number of pathogenic bacteria (unclassified_f_Ruminococcaceae, unclassified_f_Oscillospiraceae and norank_f_norank_o_Clostridia_vadinBB60_group). Overall, Vy supplementation effectively ameliorated LPS-induced intestinal damage by regulating the NF-κB-NLRP3/Nrf2-MAPK signaling pathway and maintaining intestinal microbiota balance. Vy supplementation can be used as a dietary supplement to protect broilers against intestinal inflammation and oxidative damage.

Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions: In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Sex and Age Differences in Ontogeny of Alloparenting: A Relation to Forebrain DRD1, DRD2, and HTR2A mRNA Expression?

Alloparenting refers to the practice of caring for the young by individuals other than their biological parents. The relationship between the dynamic changes in psychological functions underlying alloparenting and the development of specific neuroreceptors remains unclear. Using a classic 10-day pup sensitization procedure, together with a pup preference and pup retrieval test on the EPM (elevated plus maze), we showed that both male and female adolescent rats (24 days old) had significantly shorter latency than adult rats (65 days old) to be alloparental, and their motivation levels for pups and objects were also significantly higher. In contrast, adult rats retrieved more pups than adolescent rats even though they appeared to be more anxious on the EPM. Analysis of mRNA expression using real-time-PCR revealed a higher dopamine D2 receptor (DRD2) receptor expression in adult hippocampus, amygdala, and ventral striatum, along with higher dopamine D1 receptor (DRD1) receptor expression in ventral striatum compared to adolescent rats. Adult rats also showed significantly higher levels of 5-hydroxytryptamine receptor 2A (HTR2A) receptor expression in the medial prefrontal cortex, amygdala, ventral striatum, and hypothalamus. These results suggest that the faster onset of alloparenting in adolescent rats compared to adult rats, along with the psychological functions involved, may be mediated by varying levels of dopamine DRD1, DRD2, and HTR2A in different forebrain regions.

Chemically Mediated Artificial Electron Transport Chain.

Electron transport chains (ETCs) are ubiquitous in nearly all living systems. Replicating the complexity and control inherent in these multicomponent systems using ensembles of small molecules opens up promising avenues for molecular therapeutics, catalyst design, and the development of innovative energy conversion and storage systems. Here, we present a noncovalent, multistep artificial electron transport chains comprising cyclo[8]pyrrole (1), a meso-aryl hexaphyrin(1.0.1.0.1.0) (naphthorosarin 2), and the small molecules I2 and trifluoroacetic acid (TFA). Specifically, we show that 1) electron transfer occurs from 1 to give I3 - upon the addition of I2, 2) proton-coupled electron transfer (PCET) from 1 to give H 3 2 •2+ and H 3 2 + upon the addition of TFA to a dichloromethane mixture of 1 and 2, and 3) that further, stepwise treatment of 1 and 2 with I2 and TFA promotes electron transport from 1 to give first I3 - and then H 3 2 •2+ and H 3 2 + . The present findings are substantiated through UV-vis-NIR, 1H NMR, electron paramagnetic resonance (EPR) spectroscopic analyses, cyclic voltammetry studies, and DFT calculations. Single-crystal structure analyses were used to characterize compounds in varying redox states.

Case report: Diagnosis and surgical treatment of delayed traumatic diaphragmatic hernia with hepatothorax and enterothorax in a small dog.

An 8-year-old castrated male teddy bear dog presented to our clinic with a persistent cough. The sick dog suffered from vehicular trauma 6 months prior to the visit and had imaging and exploratory laparotomy. Imaging and exploratory laparotomy at the time showed no significant damage. We performed contrast radiography (barium gavage) on the sick dog. Based on the results of a complete contrast radiography (barium gavage), tubular shadows in the thoracic cavity were identified as the small intestine and cecum, and delayed traumatic diaphragmatic hernia with hepatothorax and enterothorax was confirmed with radiographs. Accordingly, the sick dog underwent general anesthesia, manual ventilation and diaphragmatic herniorrhaphy by standard ventral midline abdominal approach. Postoperatively, the dog was given analgesia and antibacterial treatment, and the liver biochemical indexes were monitored to prevent endotoxin. Postoperative radiographs revealed clear contours of thoracic and abdominal organs. The dog moved, ate, and urinated normally within 10 days of the surgery. This case provides a reference for a complete barium meal imaging procedure that clearly shows the position of the organs in the thoracoabdominal cavity after the occurrence of a delayed traumatic diaphragmatic hernia. This paper provides a practical reference for the diagnosis of delayed traumatic diaphragmatic hernia with hepatothorax and enterothorax.

Prevalence of skin diseases among elderly prisoners in Taiwan: an examination of skin health in prison.

BACKGROUND: Although prisoner health is a topic of significant importance, it has received limited attention in epidemiological studies, likely due to challenges in obtaining data. Therefore, this study aimed to investigate the prevalence of skin diseases among elderly prisoners in Taiwan. METHODS: We examined the presence of skin diseases in 2215 elderly prisoners based on the International Classification of Diseases, 9th revision Clinical Modification (ICD-9-CM). Additionally, the most common types of skin diseases among elderly prisoners in Taiwan were identified. RESULTS: The prevalence of skin diseases among prisoners was estimated to be 55.03%. Elderly men prisoners exhibited a higher prevalence of skin diseases than the women prisoners. The most common skin diseases observed were as follows: contact dermatitis and other forms of eczema; pruritus and related conditions; cellulitis and abscesses; and urticaria. CONCLUSION: Skin diseases were identified in more than half of the elderly prisoners. The overall quality of life of elderly prisoners can be improved by addressing their skin health, which would contribute to the fulfilment of their basic human rights. CLINICAL TRIALS NUMBER: NA.

Self-perceived knowledge, attitude, and practice of evidence-based medicine before and after training among healthcare workers in Taizhou, China.

BACKGROUND: Evidence-based medicine (EBM) is the combination of the best research evidence with our clinical expertise, specific situations, and the unique values of our patients. It is essential to evaluate the effectiveness of EBM training for healthcare workers (HCWs). OBJECTIVES: This study aims to assess the impact of EBM training on HCWs' knowledge, attitude, and practice (KAP) related to EBM. METHODS: A self-reported online survey was carried out to investigate KAP related to EBM among HCWs at a tertiary hospital in Taizhou, China. HCWs participated in EBM training on 9 and 10 September 2023. The questionnaire survey was conducted to understand KAP related to EBM before and after the training, and to compare and analyze the results before and after the training. The R software (version 4.1.0) was used to analyze data. RESULTS: Sixty-four HCWs completed the survey with a response rate of 52.5% (64/122). The overall average scores of KAP related to EBM before training were 55.3, 63.0, and 34.5, respectively, and 56.9, 66.5, and 34.7 were the scores of KAP after training. HCWs' scores of knowledge (P = 0.033) and attitude (P < 0.001) related to EBM improved significantly after the training. CONCLUSION: This study implied that EBM training may improve the knowledge and attitude of HCWs, and its teaching effect is considerable.

The transcription factor MhZAT10 enhances antioxidant capacity by directly activating the antioxidant genes MhMSD1, MhAPX3a, and MhCAT1 in apple rootstock SH6 (Malus honanensis × M. domestica).

Stress tolerance in apple (Malus domestica) can be improved by grafting to a stress-tolerant rootstock, such as 'SH6' (Malus honanensis × M. domestica 'Ralls Genet'). However, the mechanisms of stress tolerance in this rootstock are unclear. In Arabidopsis (Arabidopsis thaliana), the transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) is a key component of plant tolerance to multiple abiotic stresses and positively regulates antioxidant enzymes. However, how reactive oxygen species (ROS) are eliminated upon activation of ZAT10 in response to abiotic stress remains elusive. Here, we report that MhZAT10 in the rootstock SH6 directly activates the transcription of three genes encoding the antioxidant enzymes MANGANESE SUPEROXIDE DISMUTASE 1 (MhMSD1), ASCORBATE PEROXIDASE 3A (MhAPX3a), and CATALASE 1 (MhCAT1) by binding to their promoters. Heterologous expression in Arabidopsis protoplasts showed that MhMSD1, MhAPX3a, and MhCAT1 localize in multiple subcellular compartments. Overexpressing MhMSD1, MhAPX3a, or MhCAT1 in SH6 fruit calli resulted in higher superoxide dismutase, ascorbate peroxidase, and catalase enzyme activities in their respective overexpressing calli than in those overexpressing MhZAT10. Notably, the calli overexpressing MhZAT10 exhibited better growth and lower ROS levels under simulated osmotic stress. Apple SH6 plants overexpressing MhZAT10 in their roots via Agrobacterium rhizogenes-mediated transformation also showed enhanced tolerance to osmotic stress, with higher leaf photosynthetic capacity, relative water content in roots, and antioxidant enzyme activity, as well as less ROS accumulation. Overall, our study demonstrates that the transcription factor MhZAT10 synergistically regulates the transcription of multiple antioxidant-related genes and elevates ROS detoxification.

Fate of antibiotic resistance genes and EPS defence mechanisms during simultaneous denitrification and methanogenesis, coupled with the biodegradation of multiple antibiotics under zinc stress.

High-strength nitrogen and antibiotics-containing wastewater can be efficiently eliminated by simultaneous denitrification and methanogenesis (SDM). Heavy metals and antibiotics are two critical factors that can lead to horizontal transfer of antibiotic resistance genes (ARGs), which can be simultaneously detected in wastewater. Unfortunately, the impacts of heavy metals on SDM and antibiotic biodegradation have not been fully elucidated. Herein, the effects of SDM and multiple antibiotics biodegradation, extracellular polymeric substances (EPSs) and protein response mechanisms, and ARG fate under Zn(II) stress were comprehensively evaluated. The results indicated that a high level of Zn(II) (≥5 mg/L) stress significantly decreased the degradation rate of multiple antibiotics and suppressed denitrification and methanogenesis. In addition, Zn(II) exposure prompted the liberation of proteins from microbes into the EPSs, and the combination of EPSs with small molecules quenched the original fluorescent components and destroyed the protein structure. The dominant proteins can bind to both Zn(II) and multiple antibiotics through several types of chemical interactions, including metallic and hydrogen bonds, hydrophobic interactions, and salt bridges, relieving the toxicity of harmful substances. Moreover, metagenomic sequencing revealed that the abundance of zinc resistance genes (Zn-RGs), ARGs (mainly tetracyclines), and mobile genetic elements (MGEs) increased under Zn(II) stress. Mantel test illustrated that the ARGs mecD, tetT, and tetB(60) were most affected by MGEs. Moreover, molecular network analysis revealed that several MGEs can bridge metal resistance genes (MRGs) and ARGs, facilitating the horizontal transfer of ARGs. This study provides theoretical guidance for the environmental risk control of antibiotics-containing wastewater treated by an SDM system.

Insights into the characteristics of changes in dissolved organic matter fluorescence components on the natural attenuation process of toluene.

Natural attenuation (NA) is of great significance for the remediation of contaminated groundwater, and how to identify NA patterns of toluene in aquifers more quickly and effectively poses an urgent challenge. In this study, the NA of toluene in two typical soils was conducted by means of soil column experiment. Based on column experiments, dissolved organic matter (DOM) was rapidly identified using fluorescence spectroscopy, and the relationship between DOM and the NA of toluene was established through structural equation modeling analysis. The adsorption rates of toluene in clay and sandy soil were 39 % and 26 %, respectively. The adsorption capacity and total NA capacity of silty clay were large. The occurrence of fluorescence peaks of protein-like components and specific products indicated the occurrence of biodegradation. Arenimonas, Acidovorax and Brevundimonas were the main degrading bacteria identified in Column A, while Pseudomonas, Azotobacter and Mycobacterium were the main ones identified in Column B. The pH, ORP, and Fe(II) were the most important factors affecting the composition of microbial communities, which in turn affected the NA of toluene. These results provide a new way to quickly identify NA of toluene.

Neutrophil-Mediated Nanozyme Delivery System for Acute Kidney Injury Therapy.

Reactive oxygen species (ROS) scavenging of nanozymes toward acute kidney injury (AKI) is a current promising strategy, however, the glomerular filtration barrier (GFB) limits their application for treating kidney related diseases. Here, a neutrophil-mediated delivery system able to hijack neutrophil to transport nanozyme-loaded cRGD-liposomes to inflamed kidney for AKI treatment by cRGD targeting integrin αvß1 is reported. The neutrophil-mediated nanozyme delivery system demonstrated great antioxidant and anti-apoptosis ability in HK-2 and NRK-52E cell lines. Moreover, in ischemia-reperfusion (I/R) induced AKI mice, a single dose of LM@cRGD-LPs 12 h post-ischemia significantly reduces renal function indicators, alleviates renal pathological changes, and inhibits apoptosis of renal tubular cells and the expression of renal tubular injured marker, thus remarkably reducing the damage of AKI. Mechanistically, the treatment of LM@cRGD-LPs markedly inhibits the process of Nrf2 to the nucleus and reduces the expression of the downstream HO-1, achieves a 99.51% increase in renal tissue Nrf2 levels, and an 86.31% decrease in HO-1 levels after LM@cRGD-LPs treatment. In short, the strategy of neutrophil-mediated nanozyme delivery system hold great promise as a potential therapy for AKI or other inflammatory diseases.

Recent Advances and Multiple Strategies of Monoterpenoid Overproduction in Saccharomyces cerevisiae and Yarrowia lipolytica.

Monoterpenoids are an important subclass of terpenoids that play important roles in the energy, cosmetics, pharmaceuticals, and fragrances fields. With the development of biotechnology, microbial synthesis of monoterpenoids has received great attention. Yeasts such Saccharomyces cerevisiae and Yarrowia lipolytica are emerging as potential hosts for monoterpenoids production because of unique advantages including rapid growth cycles, mature gene editing tools, and clear genetic background. Recently, advancements in metabolic engineering and fermentation engineering have significantly enhanced the accumulation of monoterpenoids in cell factories. First, this review introduces the biosynthetic pathway of monoterpenoids and comprehensively summarizes the latest production strategies, which encompass enhancing precursor flux, modulating the expression of rate-limited enzymes, suppressing competitive pathway flux, mitigating cytotoxicity, optimizing substrate utilization, and refining the fermentation process. Subsequently, this review introduces four representative monoterpenoids. Finally, we outline the future prospects for efficient construction cell factories tailored for the production of monoterpenoids and other terpenoids.

The Association of Cerebral Oxygen Desaturation with Postoperative Cognitive Dysfunction in Older Patients: A Review.

Postoperative cognitive dysfunction (POCD) is a neurological complication associated with surgery and anesthesia that is commonly observed in older patients, and it can significantly affect patient prognosis and survival. Therefore, predicting and preventing POCD is important. Regional cerebral oxygen saturation (rSO2) reflects cerebral perfusion and oxygenation, and decreased intraoperative cerebral oxygen saturation has been reported to increase the risk of POCD. In this review, we elucidated the important relationship between the decline in rSO2 and risk of POCD in older patients. We also emphasized the importance of monitoring rSO2 during surgery to predict and prevent adverse perioperative cognitive outcomes. The findings reveal that incorporating intraoperative rSO2 monitoring into clinical practice has potential benefits, such as protecting cognitive function, reducing perioperative adverse outcomes, and ultimately improving the overall quality of life of older adults.

Real-World Effectiveness and Safety of Tixagevimab-Cilgavimab: A Target Trial Emulation Study.

BACKGROUND: Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited. OBJECTIVE: The aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals. METHODS: Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not. RESULTS: A total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history. CONCLUSIONS: Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection.