LiNAC100 contributes to linalool biosynthesis by directly regulating LiLiS in Lilium 'Siberia'.

MAIN CONCLUSION: The transcription factor LiNAC100 has a novel function of regulating floral fragrance by directly regulating linalool synthase gene LiLiS. Lilium 'Siberia', an Oriental hybrid, is renowned as both a cut flower and garden plant, prized for its color and fragrance. The fragrance comprises volatile organic compounds (VOCs), primarily monoterpenes found in the plant. While the primary terpene synthases in Lilium 'Siberia' were identified, the transcriptional regulation of these terpene synthase (TPS) genes remains unclear. Thus, understanding the regulatory mechanisms of monoterpene biosynthesis is crucial for breeding flower fragrance, thereby improving ornamental and commercial values. In this study, we isolated a nuclear-localized LiNAC100 transcription factor from Lilium 'Siberia'. The virus-induced gene silencing (VIGS) of LiNAC100 was found to down-regulate the expression of linalool synthase gene (LiLiS) and significantly inhibit linalool synthesis. Conversely, transient overexpression of LiNAC100 produced opposite effects. Additionally, yeast one-hybrid and dual-luciferase assays confirmed that LiNAC100 directly activates LiLiS expression. Our findings reveal that LiNAC100 plays a key role in monoterpene biosynthesis in Lilium 'Siberia', promoting linalool synthesis through the activation of LiLiS expression. These results offer insights into the molecular mechanisms of terpene biosynthesis in Lilium 'Siberia' and open avenues for biotechnological enhancement of floral scent.

Global, regional and national trends and impacts of natural floods, 1990-2022.

Objective: To assess global, regional and national trends in the impact of floods from 1990 to 2022 and determine factors influencing flood-related deaths. Methods: We used data on flood disasters from the International Disaster Database for 1990-2022 from 168 countries. We calculated the annual percentage change to estimate trends in the rates of people affected and killed by floods by study period, World Health Organization (WHO) region, country income level and flood type. We used multivariable logistic regression analysis to assess the factors associated with death from floods. Findings: From 1990 to 2022, 4713 floods were recorded in 168 countries, which affected > 3.2 billion people, caused 218 353 deaths and were responsible for more than 1.3 trillion United States dollars of economic losses. The WHO Western Pacific Region had the most people affected by floods (> 2.0 billion), accounting for 63.19% (2 024 599 380/3 203 944 965) of all affected populations. The South-East Asia Region had the most deaths (71 713, 32.84%). The African and Eastern Mediterranean Regions had the highest number of people affected and killed by floods per 100 000 population in 2022. The odds of floods causing more than 50 deaths were significantly higher in low-income countries (adjusted odds ratio: 14.34; 95% confidence interval: 7.46 to 30.04) compared with high-income countries. Numbers of people affected and mortality due to floods declined over time. Conclusion: Despite the decreases in populations affected and deaths, floods still have a serious impact on people and economies globally, particularly in lower-income countries. Action is needed to improve disaster risk management and flood mitigation.

Design and Asymmetric Control of Orientational Chirality by Using the Combination of C(sp2)-C(sp) Levers and Achiral N-Protecting Group.

New chiral targets of orientational chirality have been designed and asymmetrically synthesized by taking advantage of N-sulfinyl imine-directed nucleophilic addition/oxidation, Suzuki-Miyaura, and Sonogashira cross-coupling reactions. Orientation of single isomers has been selectively controlled by using aryl/alkynyl levers [C(sp2)-C(sp) axis] and tBuSO2- protecting group on nitrogen as proven by X-ray diffraction analysis. The key structural characteristic of resulting orientational products is shown by remote through-space blocking manner. Seventeen examples of multi-step synthesis were obtained with modest to good chemical yields and complete orientational selectivity.

Discovery of highly potent PARP7 inhibitors for cancer immunotherapy.

PARP7 has been proven to play an important role in immunity. Substantial upregulation of PARP7 is observed in numerous cancerous cell types, consequently resulting in the inhibition of type Ⅰ interferon signaling pathways. Therefore, inhibiting the activity of PARP7 can enhance type Ⅰ interferon signaling to exert an anti-tumor immune response. In this study, we reported the identification of a newly found PARP7 inhibitor (XLY-1) with higher inhibitory activity (IC50 = 0.6 nM) than that of RBN-2397 (IC50 = 6.0 nM). Additionally, XYL-1 displayed weak inhibitory activity on PARP1 (IC50 > 1.0 µM). Mechanism studies showed that XYL-1 could enhance the type Ⅰ interferon signaling in vitro. Pharmacodynamic experiments showed that 50 mg/kg XYL-1 could significantly inhibit tumor growth (TGI: 76.5 %) and related experiments showed that XYL-1 could restore type Ⅰ interferon signaling and promote T cell infiltration in tumor tissues. Taken together, XYL-1 shows promise as a potential candidate for developing cancer immunotherapy agents.

Expansion of YALIcloneHR toolkit for Yarrowia lipolytica combined with Golden Gate and CRISPR technology.

Metabolic Engineering of yeast is a critical approach to improving the production capacity of cell factories. To obtain genetically stable recombinant strains, the exogenous DNA is preferred to be integrated into the genome. Previously, we developed a Golden Gate toolkit YALIcloneNHEJ, which could be used as an efficient modular cloning toolkit for the random integration of multigene pathways through the innate non-homologous end-joining repair mechanisms of Yarrowia lipolytica. We expanded the toolkit by designing additional building blocks of homologous arms and using CRISPR technology. The reconstructed toolkit was thus entitled YALIcloneHR and designed for gene-specific knockout and integration. To verify the effectiveness of the system, the gene PEX10 was selected as the target for the knockout. This system was subsequently applied for the arachidonic acid production, and the reconstructed strain can accumulate 4.8% of arachidonic acid. The toolkit will expand gene editing technology in Y. lipolytica, which would help produce other chemicals derived from acetyl-CoA in the future.

C(sp)-C(sp) Lever-Based Targets of Orientational Chirality: Design and Asymmetric Synthesis.

In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of N-sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking. Forty examples of multi-step synthesis were performed, with modest to good yields and excellent orientational selectivity. Several chiral orientational amino targets are attached with scaffolds of natural and medicinal products, showing potential pharmaceutical and medical applications in the future.

Association between public attention and monkeypox epidemic: A global lag-correlation analysis.

The human monkeypox has become a public health problem globally. Google Trends Index (GTI) is an indicator of public attention, being potential for infectious disease outbreak surveillance. In this study, we used lag-correlation analysis to evaluate the spearman correlation coefficients between public attention and monkeypox epidemic by -36 to +36 days-lag in top 20 countries with most cumulated cases until September 30, 2022, the meta-analyses were performed to pool the coefficients of countries among all lags. We also constructed vector autoregression model and Granger-causality test to probe the significance of GTI in monkeypox forecasting. The strongest spearman correlation was found at lag +13 day (r = 0.53, 95% confidence interval: 0.371-0.703, p < 0.05). Meta-analysis showed significantly positive correlation when the lag was from -12 to +36 day, which was most notable on the third posterior day (lag +3 day). The pooled spearman correlation coefficients were all above 0.200 when the lag ranged from +1 to +20 day, and the causality of GTI for daily case was significant in worldwide and multiple countries. The findings suggested a robust association between 13-days-priority GTI and daily cases worldwide. This work introduced a potential monitor indicator on the early warning and surveillance of monkeypox outbreak.

Trends and disparities in 44 national notifiable infectious diseases in China: An analysis of national surveillance data from 2010 to 2019.

Research assessing the changing epidemiology of infectious diseases in China after the implementation of new healthcare reform in 2009 was scarce. We aimed to get the latest trends and disparities of national notifiable infectious diseases by age, sex, province, and season in China from 2010 to 2019. The number of incident cases and deaths, incidence rate, and mortality of 44 national notifiable infectious diseases by sex, age groups, and provincial regions from 2010 to 2019 were extracted from the China Information System for Disease Control and Prevention and official reports and divided into six kinds of infectious diseases by transmission routes and three classes (A-C) in this descriptive study. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends of incidence and mortality rate. We calculated the concentration index to measure economic-related inequality. Segmented interrupted time-series analysis was used to estimate the impact of the COVID-19 pandemic on the epidemic of notifiable infectious diseases. The trend of incidence rate on six kinds of infectious diseases by transmission routes was stable, while only mortality of sexual, blood-borne, and mother-to-child-borne infectious diseases increased from 0.6466 per 100 000 population in 2010 to 1.5499 per 100 000 population in 2019 by 8.76% per year (95% confidence interval [CI]: 6.88-10.68). There was a decreasing trend of incidence rate on Class-A infectious diseases (EAPC = -16.30%; 95% CI: -27.93 to -2.79) and Class-B infectious diseases (EAPC = -1.05%; 95% CI: -1.56 to -0.54), while an increasing trend on Class-C infectious diseases (EAPC = 6.22%; 95% CI: 2.13-10.48). For mortality, there was a decreasing trend on Class-C infectious diseases (EAPC = -14.76%; 95% CI: -23.46 to -5.07), and an increasing trend on Class-B infectious diseases (EAPC = 4.56%; 95% CI: 2.44-6.72). In 2019, the infectious diseases with the highest incidence rate and mortality were respiratory diseases (340.95 per 100 000 population), and sexual, blood-borne, and mother-to-child-borne infectious diseases (1.5459 per 100 000 population), respectively. The greatest increasing trend of incidence rate was observed in seasonal influenza, from 4.83 per 100 000 population in 2010 to 253.36 per 100 000 population in 2019 by 45.16% per year (95% CI: 29.81-62.33), especially among females and children aged 0-4 years old. The top disease with the highest mortality was still AIDs, which had the highest average yearly mortality in 24 provinces from 2010 to 2019, and its incidence rate (EAPC = 14.99%; 95% CI: 8.75-21.59) and mortality (EAPC = 9.65; 95%CI: 7.71-11.63) both increased from 2010 to 2019, especially among people aged 44-59 years old and 60 or older. Male incidence rate and mortality were higher than females each year from 2010 to 2018 on 29 and 10 infectious diseases, respectively. Additionally, sex differences in the incidence and mortality of AIDS were becoming larger. The curve lay above the equality line, with the negative value of the concentration index, which indicated that economic-related health disparities exist in the distribution of incidence rate and mortality of respiratory diseases (incidence rate: the concentration index = -0.063, p < 0.0001; mortality: the concentration index = -0.131, p < 0.001), sexual, blood-borne, and mother-to-child-borne infectious diseases (incidence rate: the concentration index = -0.039, p = 0.0192; mortality: the concentration index = -0.207, p < 0.0001), and the inequality disadvantageous to the poor (pro-rich). Respiratory diseases (Dec-Jan), intestinal diseases (May-Jul), zoonotic infectious diseases (Mar-Jul), and vector-borne infectious diseases (Sep-Oct) had distinct seasonal epidemic patterns. In addition, segmented interrupted time-series analyses showed that, after adjusting for potential seasonality, autocorrelation, GDP per capita, number of primary medical institutions, and other factors, there was no significant impact of COVID-19 epidemic on the monthly incidence rate of six kinds of infectious diseases by transmission routes from 2018 to 2020 (all p > 0.05). The incidence rates of six kinds of infectious diseases were stable in the past decade, and incidence rates of Class-A and Class-B infectious diseases were decreasing because of comprehensive prevention and control measures and a strengthened health system after the implementation of the new healthcare reform in China since 2009. However, age, gender, regional, and economic disparities were still observed. Concerted efforts are needed to reduce the impact of seasonal influenza (especially among children aged 0-4 years old) and the mortality of AIDs (especially among people aged 44-59 years old and 60 or older). More attention should be paid to the disparities in the burden of infectious diseases.

Study on the Mechanism of Ru-Catalyzed Cyclization of Aromatic Amides with Allylphosphine Oxides.

The mechanism of Ru-catalyzed cyclization of aromatic amides with allylphosphine oxides is studied by density functional theory calculation (DFT). The results show that, first, a 5-membered Ru ring intermediate is formed by N-H and C-H diprotons via the concerted metalation-deprotonation mechanism (CMD) and then the allylphosphine oxide is inserted through the ring-extending reaction to form a 7-membered ring intermediate. Next, reduction elimination is followed via intramolecular hydrogen transfer isomerization. At last, with the assistance of acetic acid, Ru (II) → Ru (IV) → Ru (II) complexes occur from the 7-membered Ru ring intermediate, and the final product is formed by reduction elimination and protonation reaction, while the catalyst is released to participate in the next cycle.

Associations among socioeconomic status, multimorbidity of non-communicable diseases, and the risk of household catastrophic health expenditure in China: a population-based cohort study.

BACKGROUND: Multimorbidity of non-communicable diseases (NCDs) is increasingly prevalent among older adults around the world, leading a higher risk of household catastrophic health expenditure (CHE). As current powerful evidence was insufficient, we aimed to estimate the association between multimorbidity of NCDs and the risk of CHE in China. METHODS: We designed a cohort study using data investigated in 2011-2018 from the China Health and Retirement Longitudinal Study, which is a nationally-representative study covering 150 counties of 28 provinces in China. We used mean ± standard deviation (SD) and frequencies and percentages to describe baseline characteristics. Person χ2 test was employed to compare the differences of baseline characteristics between households with and without multimorbidity. Lorenz curve and concentration index were used to measure the socioeconomic inequalities of CHE incidence. Cox proportional hazards models were applied to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association between multimorbidity and CHE. RESULTS: Among 17,708 participants, 17,182 individuals were included for the descriptive analysis of the prevalence of multimorbidity in 2011, and 13,299 individuals (8029 households) met inclusion criteria and were included in the final analysis with a median of 83 (interquartile range: 25-84) person-months of follow-up. 45.1% (7752/17,182) individuals and 56.9% (4571/8029) households had multimorbidity at baseline. Participants with higher family economic level (aOR = 0.91, 95% CI: 0.86-0.97) had lower multimorbidity prevalence than those with lowest family economic level. 82.1% of participants with multimorbidity did not make use of outpatient care. The CHE incidence was more concentrated among participants with higher socioeconomic status (SES) with a concentration index of 0.059. The risk of CHE was 19% (aHR = 1.19, 95% CI: 1.16-1.22) higher for each additional NCD. CONCLUSIONS: Approximately half of middle-aged and older adults in China had multimorbidity, causing a 19% higher risk of CHE for each additional NCD. Early interventions for preventing multimorbidity among people with low SES could be intensified to protect older adults from financial hardship. In addition, concerted efforts are needed to increase patients' rational healthcare utilization and strengthen current medical security for people with high SES to reduce economic disparities in CHE.

Increasing incidence rates of sexually transmitted infections from 2010 to 2019: an analysis of temporal trends by geographical regions and age groups from the 2019 Global Burden of Disease Study.

BACKGROUND: World Health Organization announced its goal of ending sexually transmitted infection (STI) epidemics by 2030. To provide a reference for tailored prevention strategies, we analyzed trends and differences in STIs by geographical regions and age groups from 1990 to 2019. METHODS: Annual number of new infections and age-standardized incidence rates (ASRs) of syphilis, chlamydia, gonorrhea, trichomoniasis, and genital herpes were recorded from the 2019 Global Burden of Disease study. We quantified the temporal trends of STIs by calculating changes in new infections and estimated annual percentage changes (EAPCs) of ASR. RESULTS: The ASRs of syphilis, chlamydia, trichomoniasis, and genital herpes increased by 1.70% (95% confidence interval [CI], 1.62-1.78%), 0.29% (95% CI 0.04-0.54%), 0.27% (95% CI 0.03-0.52%), and 0.40% (95% CI 0.36-0.44%) per year from 2010 to 2019 worldwide, respectively, while that of gonorrhea did not. The American regions had the greatest increase in ASR for syphilis (tropical Latin America: EAPC, 5.72; 95% CI 5.11-6.33), chlamydia (high-income North America: EAPC, 1.23; 95% CI 0.73-1.73), and gonorrhea (high-income North America: EAPC, 0.77; 95% CI 0.12-1.41). Additionally, southern sub-Saharan Africa and East Asia had the greatest increase in ASR for trichomoniasis (EAPC, 0.88; 95% CI 0.57-1.20) and genital herpes (EAPC, 1.44; 95% CI 0.83-2.06), respectively. In the most recent years, the population with the greatest incidence of syphilis tended to be younger globally (25-29 years in 2010 vs. 20-24 years in 2019) but older in North Africa and Middle East (20-24 year vs. 25-29 years); with chlamydia tended to be older in southern sub-Saharan Africa (25-29 years vs. 30-34 years) but younger in Australasia (40-44 years vs. 25-29 years); with genital herpes tended to be older in high-income North America (20-24 years vs. 25-29 years) and South Asia (25-29 years vs. 30-34 years). CONCLUSIONS: Syphilis, chlamydia, trichomoniasis, and genital herpes showed a trend of increasing ASR from 2010 to 2019. The differences in trends by geographical regions and age groups point to the need for more targeted prevention strategies in key regions and populations.

Bergenin, a PPARγ agonist, inhibits Th17 differentiation and subsequent neutrophilic asthma by preventing GLS1-dependent glutaminolysis.

Bergenin is a natural PPARγ agonist that can prevent neutrophil aggregation, and often be used in clinics for treating respiratory diseases. Recent data show that Th17 cells are important for neutrophil aggregation and asthma through secreting IL-17A. In this study, we investigated the effects of bergenin on Th17 differentiation in vitro and subsequent neutrophilic asthma in mice. Naïve T cells isolated from mouse mesenteric lymph nodes were treated with IL-23, TGF-ß, and IL-6 to induce Th17 differentiation. We showed that in naïve T cells under Th17-polarizing condition, the addition of bergenin (3, 10, 30 µM) concentration-dependently decreased the percentage of CD4+ IL-17A+ T cells and mRNA expression of specific transcription factor RORγt, and function-related factors IL-17A/F, IL-21, and IL-22, but did not affect the cell vitality and apoptosis. Furthermore, bergenin treatment prevented GLS1-dependent glutaminolysis in the progress of Th17 differentiation, slightly affected the levels of SLC1A5, SLC38A1, GLUD1, GOT1, and GPT2. Glutamine deprivation, the addition of glutamate (1 mM), α-ketoglutarate (1 mM), or GLS1 plasmid all significantly attenuated the above-mentioned actions of bergenin. Besides, we demonstrated that bergenin (3, 10, and 30 µM) concentration-dependently activated PPARγ in naïve T cells, whereas PPARγ antagonist GW9662 and siPPARγ abolished bergenin-caused inhibition on glutaminolysis and Th17 differentiation. Furthermore, we revealed that bergenin inhibited glutaminolysis by regulating the level of CDK1, phosphorylation and degradation of Cdh1, and APC/C-Cdh1-mediated ubiquitin-proteasomal degradation of GLS1 after activating PPARγ. We demonstrated a correlation existing among bergenin-affected GLS1-dependent glutaminolysis, PPARγ, "CDK1-APC/C-Cdh1" signaling, and Th17 differentiation. Finally, the therapeutic effect and mechanisms for bergenin-inhibited Th17 responses and neutrophilic asthma were confirmed in a mouse model of neutrophilic asthma by administration of GW9662 or GLS1 overexpression plasmid in vivo. In conclusion, bergenin repressed Th17 differentiation and then alleviated neutrophilic asthma in mice by inhibiting GLS1-dependent glutaminolysis via regulating the "CDK1-APC/C-Cdh1" signaling after activating PPARγ.

The effect of physical activity interventions on cognition function in patients with diabetes: A systematic review and meta-analysis.

BACKGROUND: In recent years, studies have revealed that cognition may be impaired by glucose metabolism disorder. Meanwhile, physical activity has been demonstrated to maintain blood glucose. This meta-analysis was conducted to assess the effect of physical activity on cognition in patients with diabetes and provide evidence for the treatment of cognition impairment among them. METHODS: We searched studies published in five databases from 1 January 1984 to 29 August 2020. A random-effect or fixed-effect meta-analysis was used to estimate the pooled effect of physical activity on the change of cognition throughout intervention duration and post-intervention cognition scores by standardized mean difference (SMD) and its 95% confidence interval (CI). We used funnel plots to evaluate the publication bias, I2 statistic to evaluate the heterogeneity and did subgroup analysis stratified by sample size and follow-up time. RESULTS: Five eligible studies involving 2581 patients with diabetes were included. The pooled effect of physical activity on cognition improvement in patients with diabetes was significant (SMD = 0.98, 95% CI: 0.34-1.62), while the effect on post-intervention cognition scores was not significant (SMD = 0.35, 95% CI: -0.04-0.73). In the subgroup analysis, the pooled effect was significantly higher in studies of follow-up time less than 1 year (SMD = 2.14, 95% CI: 1.63-2.64), while observing no significant effect in studies of follow-up time over 1 year (SMD = 0.10, 95% CI: -0.11-0.32). CONCLUSIONS: Physical activity is beneficial to improving cognition in patients with diabetes. However, the long-term effect needs to be explored in future studies.

Internet use and need for digital health technology among the elderly: a cross-sectional survey in China.

BACKGROUND: China is becoming an aging society at the fastest pace in history, and there are a large number of empty nesters in the country. With economic and social development, internal support systems among families are gradually weakening. Supporting the elderly is thus emerging as a significant issue, and promoting digital health technologies is an effective way to help address it. Encouraging the application of Internet to elderly care and Internet use among the elderly are important means of promoting digital health technologies. This paper examines the current state of the use of the Internet by the elderly and factors influencing it (including physical, psychological, and social) as well as demand among the elderly for smart services. METHODS: A total of 669 subjects over the age of 60 years were randomly selected from 13 cities in Heilongjiang province and surveyed using questionnaires from May 1 to July 31, 2018. The questionnaires were collected for descriptive statistics, the chi-square test, and the analysis of influential factors. RESULTS: Of the people surveyed, 38.6% used the Internet. Their favorite online activity was online dating (74.2%), and the health information they obtained through the Internet was mainly related to diet (63.1%) and exercise (47.1%). The subjects demanded smart bracelets (MD = 2.80) and emergency callers (MD = 2.77). Gender, age, education, monthly income, quality of life, number of friends, and social participation were found to have an impact on Internet use. CONCLUSIONS: More measures are needed to reduce barriers to the use of the Internet and promote digital health technologies. The society, equipment manufacturers, and family members of the elderly should work together to enable them to reap the benefits of online technologies.

Alpinetin improves intestinal barrier homeostasis via regulating AhR/suv39h1/TSC2/mTORC1/autophagy pathway.

The injury of intestinal epithelial barrier is considered as the key pathophysiological process in response to gastrointestinal infection and inflammation, and plays an important role in the initiation and development of colitis. Alpinetin has been shown to improve intestinal barrier homeostasis under colitis condition, but the mechanism is still unclear. Here, we showed that alpinetin significantly improved transepithelial electrical resistance (TEER) in TNF-α-stimulated Caco-2 cells, which was mainly mediated by inhibiting the apoptosis. Mechanistic studies demonstrated that alpinetin markedly increased the production of autophagosomes, along with obvious regulation of LC3B-II, beclin-1, p62, Atg7 and Atg5 expressions. In addition, it also markedly repressed the activation of mTORC1 signaling pathway, which was ascribed to TSC2 rather than p-AKT, p-ERK, p-AMPKα or PTEN expressions in Caco-2 and NCM460 cells. Furthermore, the enrichment of H3K9me3 at TSC2 promoter region was decreased and ubiquitin proteasome degradation of suv39h1 was increased. Additionally, alpinetin activated aryl hydrocarbon receptor (AhR) and promoted co-localization of AhR with suv39h1 in the cytoplasm. The relationship between alpinetin-regulated AhR/suv39h1/TSC2/mTORC1 signals, autophagy and apoptosis of Caco-2 and NCM460 cells was confirmed by using CH223191, siAhR, siTSC2 and chloroquine. Finally, CH223191 and leucine abolished alpinetin-mediated inhibition of intestinal epithelial cells apoptosis, improvement of intestinal epithelial barrier and amelioration of colitis.

Effects of IRW and IQW on Oxidative Stress and Gut Microbiota in Dextran Sodium Sulfate-Induced Colitis.

BACKGROUND/AIMS: There are known links between inflammatory bowel disease (IBD) and changes in the microbiota of the gut and inflammation and oxidative stress. In this study, a colitis model induced by dextran sodium sulfate (DSS) in mice is used to evaluate whether the presence of bioactive peptides IRW (Ile-Arg-Trp) and IQW (Ile-Gln-Trp) peptides is advantageous. METHODS: The mice were arbitrarily assigned to the following four groups: (i) control (untreated), (ii) dextran sodium sulfate (DSS) treated, (iii) IRW-DSS treated, and (iv) IQW-DSS treated. For 7 days, the control group subjects had unrestricted access to untreated drinking water, whereas the drinking water supplied to the subjects in the DSS, IRW-DSS, and IQW-DSS groups during this period consisted of 5% DSS solution. The colonic lesions were scored after hematoxylin and eosin staining. Serum antioxidant capacity was analyzed by 2,2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) radical cation decolorization test and the microbiota in the colonic contents were sequenced by HiSeq2500 PE250. RESULTS: The presence of DSS reduced daily weight gain, enhanced histopathology scores, and inhibited antioxidant enzyme expression. Superoxide dismutase, catalase, and glutathione peroxidase activities in the DSS-induced colitis model were significantly enhanced (P < 0.05) in the presence of dietary IRW and IQW. Furthermore, the Simpson index was significantly increased (P < 0.05) in the presence of dietary IRW and IQW compared to the control group. IRW and IQW increased the abundance of Coprococcus_1, Ruminococcaceae_UCG-014, and Desulfovibrio compared to the control group and DSS group. Furthermore, IQW decreased the abundance of Bacteroides in relation to the control group, but increased Parabacteroides. In addition, IRW increased the level of Anaerotruncus, Oscillibacter, and Ruminiclostridium_9 compared to the control group. CONCLUSION: This study concludes that the presence of IRW or IQW can mitigate DSS-induced oxidative stress by improving the activities of antioxidant enzymes, increasing intestinal microbial diversity and enhancing the abundance of gut microbiota, which may help maintain the homeostasis of host health and microenvironment in a DSS-induced mouse model, thus providing a potential further treatment for IBD patients.

Hyperhomocysteinemia and cardiovascular disease in animal model.

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease and is associated with primary causes of mortality and morbidity throughout the world. Several studies have been carried out to evaluate the effects of a diet inducing cystathionine-ß-synthase, methyltetrafolate, folic acid, and vitamin B supplemented with methionine on the homocysteine metabolism and in lowering the plasma total homocysteine levels. A large number of molecular and biomedical studies in numerous animals, such as mice, rabbits, and pigs, have sought to elevate the plasma total homocysteine levels and to identify a disease model for human hyperhomocysteinemia. However, a specific animal model is not suitable for hyperhomocysteinemia in terms of all aspects of cardiovascular disease. In this review article, the experimental progress of animal models with plasma total homocysteine levels is examined to identify a feasible animal model of hyperhomocysteinemia for different aspects.

The role of methionine on metabolism, oxidative stress, and diseases.

Methionine is an aliphatic, sulfur-containing, essential amino acid, and a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals. It also intervenes in lipid metabolism, activation of endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and the biosynthesis of glutathione to counteract oxidative stress. In addition, methionine restriction prevents altered methionine/transmethylation metabolism, thereby decreasing DNA damage and carcinogenic processes and possibly preventing arterial, neuropsychiatric, and neurodegenerative diseases. This review focuses on the role of methionine in metabolism, oxidative stress, and related diseases.

Association of temperature and precipitation with malaria incidence in 57 countries and territories from 2000 to 2019: A worldwide observational study.

Background: The transmission of malaria is known to be affected by climatic factors. However, existing studies on the impact of temperature and precipitation on malaria incidence offer no clear-cut conclusions, and there is a lack of research on a global scale. We aimed to estimate the association of temperature and precipitation with malaria incidence globally from 2000 to 2019. Methods: We used meteorological data from the National Centers for Environmental Information and malaria incidence data from the Global Burden of Disease Study 2019 to calculate effect sizes through quasi-Poisson generalised linear models while controlling for confounders. Results: 231.4 million malaria cases occurred worldwide in 2019. National annual average temperature and precipitation were associated with malaria incidence, with an increase in the age-standardised incidence rate (ASIR) of 2.01% (95% confidence interval (CI) = 2.00, 2.02) and 6.04% (95% CI = 6.00, 6.09) following one unit increase of national annual average temperature and precipitation. In subgroup analysis, we found that malaria incidence in Asian countries was most affected by temperature, while the incidence in African countries was most affected by precipitation (P < 0.05). Stratified by age, children under five were most affected by both temperature and precipitation (P < 0.05). We additionally found that the impact of the national annual average temperature on malaria incidence increased over time (P < 0.05). Conclusions: We advocate for a comprehensive approach to malaria prevention, focussed on addressing the impact of climate factors through international collaboration, adaptive measures, and targeted interventions for vulnerable populations.

Advanced strategies in high-throughput droplet screening for enzyme engineering.

Enzymes, as biocatalysts, play a cumulatively important role in environmental purification and industrial production of chemicals and pharmaceuticals. However, natural enzymes are limited by their physiological properties in practice, which need to be modified driven by requirements. Screening and isolating certain enzyme variants or ideal industrial strains with high yielding of target product enzymes is one of the main directions of enzyme engineering research. Droplet-based high-throughput screening (DHTS) technology employs massive monodisperse emulsion droplets as microreactors to achieve single strain encapsulation, as well as continuous monitoring for the inside mutant library. It can effectively sort out strains or enzymes with desired characteristics, offering a throughput of 108 events per hour. Much of the early literature focused on screening various engineered strains or designing signalling sorting strategies based on DHTS technology. However, the field of enzyme engineering lacks a comprehensive overview of advanced methods for microfluidic droplets and their cutting-edge developments in generation and manipulation. This review emphasizes the advanced strategies and frontiers of microfluidic droplet generation and manipulation facilitating enzyme engineering development. We also introduce design for various screening signals that cooperate with DHTS and devote to enzyme engineering.