Effects of Yeast Culture on Laying Performance, Antioxidant Properties, Intestinal Morphology, and Intestinal Flora of Laying Hens.

Yeast culture (YC) plays a significant role in enhancing the performance and health of poultry breeding. This study investigated the impact of different YC supplementation concentrations (basal diet with 1.0 g/kg and 2.0 g/kg of YC, YC1.0, and YC2.0) on egg production performance, egg quality, antioxidant properties, intestinal mucosal structure, and intestinal flora of laying hens. Both YC1.0 and YC2.0 groups significantly enhanced the egg protein height, Haugh unit, and crude protein content of egg yolks compared to the control group (p < 0.05). The supplementation with YC2.0 notably increased the egg production rate, reduced feed-to-egg ratio, and decreased the broken egg rate compared to the control group (p < 0.05). Additionally, YC supplementation enhanced serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity while reducing malondialdehyde (MDA) content (p < 0.05). Moreover, YC supplementation promoted duodenal villus height and villus ratio in the duodenum and jejunum (p < 0.05). Analysis of cecal microorganisms indicated a decrease in Simpson and Shannon indices with YC supplementation (p < 0.05). YC1.0 reduced the abundance of Proteobacteria, while YC2.0 increased the abundance of Bacteroidales (p < 0.05). Overall, supplementation with YC improved egg production, quality, antioxidant capacity, intestinal morphology, and cecal microbial composition in laying hens, with significant benefits observed at the 2.0 g/kg supplementation level.

NHX5/NHX6/SPY22 complex regulates BRI1 and brassinosteroid signaling in Arabidopsis.

NHX5 and NHX6, Arabidopsis endosomal antiporters, play a vital role in facilitating ion and pH homeostasis in endosomal compartments. Studies have found that NHX5 and NHX6 are essential for protein trafficking, auxin homeostasis, and plant growth and development. Here, we report the role of NHX5 and NHX6 in brassinosteroid (BR) signaling. We found that hypocotyl growth was enhanced in nhx5 nhx6 under epibrassinolide (eBR) treatment. nhx5 nhx6 bri1 was insensitive to eBR treatment, indicating that NHX5 and NHX6 are downstream of the BRI1 receptor in BR signaling. Moreover, confocal observation with both hypocotyls and root tips showed that BRI1-YFP localization in the plasma membrane (PM) was reduced in nhx5 nhx6. Interestingly, brefeldin A (BFA) treatment showed that formation of the BFA bodies containing BRI1 and their disassembling were disrupted in nhx5 nhx6. Further genetic analysis showed that NHX5/NHX6 and SYP22 may act coordinately in BR signaling. NHX5 and NHX6 may regulate SYP22 function by modulating cellular K+ and pH homeostasis. Importantly, NHX5 and NHX6 colocalize and interact with SYP22, but do not interact with BRI1. In summary, our findings indicate that NHX5/NHX6/SYP22 complex is essential for the regulation of BRI1 recycling and PM localization. The H+-leak facilitated by NHX5 and NHX6 offers a means of controlling BR signaling in plants.

Leisure-time physical activity and the incidence of atrial fibrillation in senior adults: a prospective cohort study.

OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.

Proteomics Clustering Research of ITRAQ Markers in Plasma of AIDS Patients with Different Chinese Medicine Syndromes.

Background: We aimed to distinguish the different Chinese medicine (CM) syndromes of acquired immune deficiency syndrome (AIDS) patients at the proteomics level. Methods: We collected AIDS patients diagnosed with different CM syndromes from Weishi County, Kaifeng City, Henan Province, China, including Qi-deficiency syndrome (named QD group) and dampness-heat syndrome (named DH group). Healthy people were collected as controls from Weishi County, Kaifeng city, Henan Province, China. The plasma from three groups were labeled with ITRAQ, LC/MC was used for protein quantitative analysis. Finally, sequence search and cluster analysis were performed. Results: Overall, 27 different proteins were found. Three proteins were up-regulated and 2 proteins down-regulated in the QD group, 11 proteins up-regulated and 13 proteins down-regulated in the DH group. Compared with DH group, there were 7 different proteins in QD group, among which 5 proteins were down-regulated and 2 proteins were up-regulated. When the target protein of DH group was up-regulated, the protein of HC group was down-regulated correspondingly. Conclusion: The significance analysis and clustering of protein results showed that DH group was significantly different from QD group and HC group at the protein level (P<0.05). However, the QD group could not be effectively distinguished from the HC group. AAT, PF4, C-reactive protein and c4bp may be used as potential biomarkers in DH group. Mass spectrometry based on feature selection can be used to classify different CM syndromes.

The signalling pathways, calcineurin B-like protein 5 (CBL5)-CBL-interacting protein kinase 8 (CIPK8)/CIPK24-salt overly sensitive 1 (SOS1), transduce salt signals in seed germination in Arabidopsis.

For plant growth under salt stress, sensing and transducing salt signals are central to cellular Na+ homoeostasis. The calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) complexes play critical roles in transducing salt signals in plants. Here, we show that CBL5, an ortholog of CBL4 and CBL10 in Arabidopsis, interacts with and recruits CIPK8/CIPK24 to the plasma membrane. Yeast cells coexpressing CBL5, CIPK8/CIPK24 and SOS1 demonstrated lesser Na+ accumulation and a better growth phenotype than the untransformed or SOS1 transgenic yeast cells under salinity. Overexpression of CBL5 improved the growth of the cipk8 or cipk24 single mutant but not the cipk8 cipk24 double mutant under salt stress, suggesting that CIPK8 and CIPK24 were the downstream targets of CBL5. Interestingly, seed germination in cbl5 was severely inhibited by NaCl, which was recovered by the overexpression of CBL5. Furthermore, CBL5 was mainly expressed in the cotyledons and hypocotyls, which are essential to seed germination. Na+ efflux activity in the hypocotyls of cbl5 was reduced relative to the wild-type under salt stress, enhancing Na+ accumulation. These findings indicate that CBL5 functions in seed germination and protects seeds and germinating seedlings from salt stress through the CBL5-CIPK8/CIPK24-SOS1 pathways.

MPZL2-a common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population.

BACKGROUND: Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss. METHODS: In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing. RESULTS: Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency. CONCLUSIONS: We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2.

Serological investigation on the prevalence of poliovirus in Guangdong province: A cross-sectional study.

In 2019, we conducted a cross-sectional study for polio virus seroprevalence in Guangdong province, China. We assessed the positivity rates of poliomyelitis NA and GMT in serum across various demographic groups, and the current findings were compared with pre-switch data from 2014. Using multistage random sampling method, four counties/districts were randomly selected per city, and within each, one general hospital and two township hospitals were chosen. Healthy individuals coming for medical checkups or vaccination were invited. A total of 1318 individual samples were collected and tested. In non-newborn population, age-dependent positivity rates ranged from 77.8% to 100% for PV1 NA and 70.3% to 98.9% for PV3 NA (p < .01). The lowest GMT values for both types (17.03 and 8.46) occurred in the 20 to <30 years age group, while peak GMTs for PV1 and PV3 were observed in 1 to <2 (340.14) and 0 to <1-year (168.90) age groups, respectively. GMTs for PV1 (P = .002) and PV3 (P = .007) in Eastern Guangdong were lower than those in the other three regions. Male participants showed higher GMTs than females (P = .016 and .033, respectively). In newborn population, both males and females showed higher PV1 NA positivity rates and GMTs compared to PV3 (p < .05). Post-switch PV3 NA positivity rates were higher than pre-switch rates (p = .016). GMTs of both PV1 and PV3 were significantly higher post-switch (p < .001). The positivity rates of NAs and GMTs remain high level, which play an important role in resisting poliomyelitis infection. Effect of the converted immunization program was more pronounced than that before.

Short-term and long-term efficacy of sublingual immunotherapy in different courses for house dust mite-induced allergic rhinitis.

PURPOSE: Sublingual immunotherapy (SLIT) has been proven to be an effective and safe treatment for patients with house dust mite (HDM)-induced allergic rhinitis (AR) to achieve short-term and long-term efficacy. This study aimed to investigate the relationship between SLIT duration and long-term efficacy. MATERIALS AND METHODS: This study involved 134 patients who underwent SLIT between 2019 and 2021 (in the 2-year group), between 2018 and 2021(in the 3-year group), or between 2017 and 2021 (in the 4-year group). The total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) and adverse events (AEs) were assessed at baseline, after treatment (2021) and one year after the treatment completion (2022). The correlation between MiniRQLQ and other indicators was also analyzed. RESULTS: After SLIT, patients in all three groups showed significant improvements in TNSS, TMS, VAS and MiniRQLQ scores (all p < 0.001). These improvements were sustained even one year after SLIT. Patients who received 3-4 years of SLIT showed significant improvement compared with those who received 2 years of SLIT in all clinical outcomes (all p < 0.01). The analysis showed positive correlations between the MiniRQLQ and TNSS, TMS, and VAS (all p < 0.001). No significant difference was observed in the AE rate in all three groups (p > 0.05). CONCLUSION: Different duration of HDM SLIT could generate various short-term and long-term clinical efficacy. The MiniRQLQ could be applied to evaluate SLIT efficacy in clinical practice.

Low-temperature catalytic oxidation of PCDD/Fs over MnCeCoOx/PPS catalytic filter.

Catalytic destruction of nitrogen oxides (NOx) combined with dust removal technique has attracted much attention, yet the application in the solid waste incineration air pollution control process is still lacking due to the complex flue gas atmosphere. In this work, the Mn-Ce-Co-Ox catalyst-coated polyphenylene sulfide (PPS) filter fiber with efficient dust removal and low-temperature polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) destruction has been prepared with a redox-precipitation method. The catalyst was uniformly grown around the PPS fiber with appropriate catalyst loading. The effects of several key operating parameters (e.g., reaction temperature, catalyst loading amount, and filtration velocity) on the catalytic efficiency were comprehensively investigated. The results show that the Mn-Ce-Co-Ox/PPS has a decomposition yield of 78.0% in PCDD/Fs and 96% in nitric oxide (NO) conversion at 200 °C. The poisoned catalytic filter exhibits a removal efficiency of 88.6% for PCDD/Fs. In addition, the catalytic filter can completely reject particles smaller than 1.0 µm with a low filtration resistance. Therefore, this efficient and energy-conserving catalytic filter shows promising applications in flue gas pollution treatments.

Screening of Ginkgo Individuals with Superior Growth Structural Characteristics in Different Genetic Groups Using Terrestrial Laser Scanning (TLS) Data.

With the concept of sustainable management of plantations, individual trees with excellent characteristics in plantations have received attention from breeders. To improve and maintain long-term productivity, accurate and high-throughput access to phenotypic characteristics is essential when establishing breeding strategies. Meanwhile, genetic diversity is also an important issue that must be considered, especially for plantations without seed source information. This study was carried out in a ginkgo timber plantation. We used simple sequence repeat (SSR) markers for genetic background analysis and high-density terrestrial laser scanning for growth structural characteristic extraction, aiming to provide a possibility of applying remote sensing approaches for forest breeding. First, we analyzed the genetic diversity and population structure, and grouped individual trees according to the genetic distance. Then, the growth structural characteristics (height, diameter at breast height, crown width, crown area, crown volume, height to living crown, trunk volume, biomass of all components) were extracted. Finally, individual trees in each group were comprehensively evaluated and the best-performing ones were selected. Results illustrate that terrestrial laser scanning (TLS) point cloud data can provide nondestructive estimates of the growth structural characteristics at fine scale. From the ginkgo plantation containing high genetic diversity (average polymorphism information content index was 0.719) and high variation in growth structural characteristics (coefficient of variation ranged from 21.822% to 85.477%), 11 excellent individual trees with superior growth were determined. Our study guides the scientific management of plantations and also provides a potential for applying remote sensing technologies to accelerate forest breeding.

Flavonoid synthesis in Lamiophlomis rotata from Qinghai-Tibet Plateau is influenced by soil properties, microbial community, and gene expression.

Lamiophlomis rotata is a medicinal plant in Qinghai-Tibet Plateau, in which flavonoid compounds are the major medicinal components. However, it remains unclear how flavonoid metabolism of L. rotata is influenced by soil properties and microbial community. In this study, we collected L. rotata seedlings and rhizosphere soils from five habitats ranging from 3750 to 4270 m of altitude and analyzed the effects of habitat conditions on flavonoid metabolism. The activities of peroxidase, cellulase, and urease were increased with altitude, while those of alkaline phosphatase, alkaline protease, and sucrase were decreased with altitude. Analysis of OTUs showed that the total number of bacterial genera was higher than that of fungal genera. The highest number of fungal genera was 132, and that of bacterial genera was 33 in Batang (BT) town in Yushu County at an altitude of 3880 m, suggesting that the fungal communities may play a critical role in L. rotata rhizosphere soils. Flavonoids in leaves and roots of L. rotata shared a similar pattern, with a trend of increasing levels with altitude. The highest flavonoid content measured, 12.94 mg/g in leaves and 11.43 mg/g in roots, was from Zaduo (ZD) County at an altitude of 4208 m. Soil peroxidases affected quercetin content in leaves of L. rotata, while the fungus Sebacina affected flavonoid content in leaves and roots of L. rotata. The expression of PAL, F3'H, FLS, and FNS genes showed a declining trend in leaves with altitude, while F3H showed an increasing trend in both leaves and roots. Overall, soil physicochemical properties and microbial community affect flavonoid metabolism in L. rotata in Qinghai-Tibet Plateau. The variations in flavonoid content and gene expression as well as their associations with soil factors revealed the complexity of the growth conditions and genetic makeup in L. rotata habitats of Qinghai-Tibet Plateau.

Nickel-Catalyzed Reductive [4 + 1] Sila-Cycloaddition of 1,3-Dienes with Dichlorosilanes.

Transition-metal-catalyzed sila-cycloaddition has been a promising tool for accessing silacarbocycle derivatives, but the approach has been limited to a selection of well-defined sila-synthons. Herein, we demonstrate the potential of chlorosilanes, which are industrial feedstock chemicals, for this type of reaction under reductive nickel catalysis. This work extends the scope of reductive coupling from carbocycle to silacarbocycle synthesis and from single C-Si bond formation to sila-cycloaddition reactions. The reaction proceeds under mild conditions and shows good substrate scope and functionality tolerance, and it offers new access to silacyclopent-3-enes and spiro silacarbocycles. The optical properties of several spiro dithienosiloles as well as structural variations of the products are demonstrated.

Plastid KEA-type cation/H+ antiporters are required for vacuolar protein trafficking in Arabidopsis.

Arabidopsis plastid antiporters KEA1 and KEA2 are critical for plastid development, photosynthetic efficiency, and plant development. Here, we show that KEA1 and KEA2 are involved in vacuolar protein trafficking. Genetic analyses found that the kea1 kea2 mutants had short siliques, small seeds, and short seedlings. Molecular and biochemical assays showed that seed storage proteins were missorted out of the cell and the precursor proteins were accumulated in kea1 kea2. Protein storage vacuoles (PSVs) were smaller in kea1 kea2. Further analyses showed that endosomal trafficking in kea1 kea2 was compromised. Vacuolar sorting receptor 1 (VSR1) subcellular localizations, VSR-cargo interactions, and p24 distribution on the endoplasmic reticulum (ER) and Golgi apparatus were affected in kea1 kea2. Moreover, plastid stromule growth was reduced and plastid association with the endomembrane compartments was disrupted in kea1 kea2. Stromule growth was regulated by the cellular pH and K+ homeostasis maintained by KEA1 and KEA2. The organellar pH along the trafficking pathway was altered in kea1 kea2. Overall, KEA1 and KEA2 regulate vacuolar trafficking by controlling the function of plastid stromules via adjusting pH and K+ homeostasis.

Seasonal variations of soil bacterial and fungal communities in a subtropical Eucalyptus plantation and their responses to throughfall reduction.

Climatic change causes obvious seasonal meteorological drought in southern China, yet there is a lack of comprehensive in situ studies on the effects of drought in Eucalyptus plantations. Here, a 50% throughfall reduction (TR) experiment was conducted to investigate the seasonal variations of soil bacterial and fungal communities and functions in a subtropical Eucalyptus plantation and their responses to TR treatment. Soil samples were collected from control (CK) and TR plots in the dry and rainy seasons and were subjected to high-throughput sequencing analysis. Results showed that TR treatment significantly reduced soil water content (SWC) in the rainy season. In CK and TR treatments, fungal alpha-diversity decreased in the rainy season while bacterial alpha-diversity did not change significantly between dry and rainy seasons. Moreover, bacterial networks were more affected by seasonal variations compared with fungal networks. Redundancy analysis showed that alkali hydrolyzed nitrogen and SWC contributed the most to the bacterial and fungal communities, respectively. Functional prediction indicated that the expression of soil bacterial metabolic functions and symbiotic fungi decreased in the rainy season. In conclusion, seasonal variations have a stronger effect on soil microbial community composition, diversity, and function compared with TR treatment. These findings could be used to develop management practices for subtropical Eucalyptus plantations and help maintain soil microbial diversity to sustain long-term ecosystem function and services in response to future changes in precipitation patterns.

Prohexadione-calcium alleviates the leaf and root damage caused by salt stress in rice (Oryza sativa L.) at the tillering stage.

Salt stress, as a principal abiotic stress, harms the growth and metabolism of rice, thus affecting its yield and quality. The tillering stage is the key growth period that controls rice yield. Prohexadione-calcium (Pro-Ca) can increase the lodging resistance of plants by reducing plant height, but its effects on rice leaves and roots at the tillering stage under salt stress are still unclear. This study aimed to evaluate the ability of foliar spraying of Pro-Ca to regulate growth quality at the rice tillering stage under salt stress. The results showed that salt stress reduced the tillering ability of the rice and the antioxidant enzyme activity in the roots. Salt stress also reduced the net photosynthetic rate (Pn), stomatal conductance (Gs) and intercellular CO2 concentration (Ci) of the rice leaves and increased the contents of osmotic regulatory substances in the leaves and roots. The application of exogenous Pro-Ca onto the leaves increased the tiller number of the rice under salt stress and significantly increased the photosynthetic capacity of the leaves. Additionally, it increased the activities of antioxidant enzymes and the AsA content. The contents of an osmotic regulation substance, malondialdehyde (MDA), and H2O2 in the leaves and roots also decreased. These results suggested that Pro-Ca can increase the tillering ability, photosynthetic capacity, osmotic adjustment substance content levels and antioxidant enzyme activity levels in rice and reduce membrane lipid peroxidation, thus improving the salt tolerance of rice at the tillering stage.

Prohexadione calcium enhances rice growth and tillering under NaCl stress.

Salt stress affects crop quality and reduces crop yields, and growth regulators enhance salt tolerance of crop plants. In this report, we examined the effects of prohexadione-calcium (Pro-Ca) on improving rice (Oryza sativa L.) growth and tillering under salt stress. We found that NaCl stress inhibited the growth of two rice varieties and increased malondialdehyde (MDA) levels, electrolyte leakage, and the activities of the antioxidant enzymes. Foliar application of Pro-Ca reduced seedling height and increased stem base width and lodging resistance of rice. Further analyses showed that Pro-Ca application reduced MDA content, electrolyte leakage, and membrane damage in rice leaves under NaCl stress. Pro-Ca enhanced the net photosynthetic rate (Pn), stomatal conductance (Gs), and intercellular CO2 concentration (Ci) of rice seedlings, while increasing the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbic acid peroxidase (APX) at the tillering stage under salt stress. Overall, Pro-Ca improves salt tolerance of rice seedlings at the tillering stage by enhancing lodging resistance, reducing membrane damages, and enhancing photosynthesis and antioxidant capacities of rice seedlings.

Joint effects of air PM2.5 and socioeconomic dimensions on posted emotions of urban green space visitors in cities experiencing population urbanization: A pilot study on 50 cities of East China.

People may perceive and expose negative sentiments in days with PM2.5 pollutions, but evidence is still insufficient about the joint effects of PM2.5 and socioeconomic factors on human sentiments. In this study, a total of 8032 facial photos of urban green space visitors were obtained from Sina Weibo in 50 cities of East China and rated for happy, sad, neutral scores and net positive emotion index (NPE; happy minus sad). Seasonal air PM2.5 concentrations were collected from days when people exposed faces in cities that were categorized to medium, large, outsize, and mega sizes according to resident populations (RPs). In summer, people posted lower sad score (11.28 %) than in winter (13.51 %; P = 0.0357) and higher NPE (35.86 %) than in autumn (30.92 %; P = 0.0009). Multivariate linear regression on natural logarithms revealed that factors of gross domestic product per capita (parameter estimate: 0.45), RP (0.59), non-production electricity consumption (0.34), and length of road transport (0.34) together generated positive contributions to posted happy score, while the total retail trade of consumer goods (-1.25) and PM2.5 (-0.50) were perceived as joint depressors on NPE. Overall, cities with more rich households and activated retail sales attracted more people who exposed smiles in weathers with PM2.5 compared to cities where local economy is reliable on heavy industry. The summertime in mega cities will be recommended to enjoy a higher frequency to perceive satisfaction due to exposure to low PM2.5.

Nickel-Catalyzed Cross-Electrophile 1,2-Silyl-Arylation of 1,3-Dienes with Chlorosilanes and Aryl Bromides.

Catalytic, three-component, cross-electrophile reactions have recently emerged as a promising tool for molecular diversification, but studies have focused mainly on the alkyl-carbonations of alkenes. Herein, the scope of this method has been extended to conjugated dienes and silicon chemistry through silylative difunctionalization of 1,3-dienes with chlorosilanes and aryl bromides. The reaction proceeds under mild conditions to afford 1,2-linear-silylated products, a selectivity that is different to those obtained from conventional methods via an intermediary of H(C)-η3 -π-allylmetal species. Preliminary mechanistic studies reveal that chlorosilane reacts with 1,3-diene first and then couples with aryl bromide.

Curcumin combined with arsenic trioxide in the treatment of acute myeloid leukemia: network pharmacology analysis and experimental validation.

PURPOSE: This study aimed to evaluate the effects of curcumin by co-administration of arsenic trioxide (As2O3) in acute myeloid leukemia (AML) treatment, using network pharmacology and experimental validation. METHODS: Using Pubchem database, Traditional Chinese Medicine Information Database (TCMID) database, and Swiss target prediction database to predict compound-related targets, AML-associated targets were determined using GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. We identify overlapping common targets by comparing Compounds-related and AML-associated targets and using these targets to perform GO and KEGG functional enrichment analyses. Subsequently, these targets were input into the STRING database, and we used Cytoscape to construct protein-protein interaction (PPI) network. Finally, we used KG1-a cells and the AML mouse model to measure the anti-leukemia effects of curcumin and As2O3 and their combination. RESULTS: Compounds and targets screening hinted that 85 intersection targets were predicted in the curcumin treatment of AML, 75 targets in the As2O3 treatment of AML, and 48 targets in the curcumin combined with the As2O3 treatment of AML. GO and KEGG analyses indicated that the top 10 enriched biological processes and top 20 pathways implicated in the therapeutic effects of curcumin and As2O3 on AML, respectively. In addition, network pharmacology screening revealed STAT3, TP53, EP300, MAPK1, and PIK3CA as the top five genes in PPI network of curcumin treatment of AML and TP53, MAPK3, MAPK1, STAT3, and SRC as the top five genes in PPI network of As2O3 treatment of AML. Moreover, the in vitro experiment demonstrated that curcumin combined with As2O3 inhibited proliferation and induced apoptosis in KG1-a cells, and this effect is more substantial than curcumin or As2O3 alone. Mechanistically, the curcumin combined with As2O3 significantly down-regulated the protein expression of JAK2, STAT3, and Bcl-2, and up-regulated the levels of P53, P27, and Bax. In the mouse model, the survival time of mice in each administration group was drawn out to varying degrees, with the most significant prolongation in the curcumin combined with the As2O3 group. CONCLUSION: Our results suggested that curcumin and As2O3 combination therapy exerts more significant anti-leukemia effects in the treatment of AML than curcumin or As2O3 monotherapy by up-regulating p53 pathway and down-regulating the JAK2/STAT3 pathway.

Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.