Characteristics associated with effectiveness in postoperative delirium research: a systematic review of randomised controlled trials with meta-regression and meta-analysis.

BACKGROUND: Postoperative delirium remains prevalent despite extensive research through randomised trials aimed at reducing its incidence. Understanding trial characteristics associated with interventions' effectiveness facilitates data interpretation. METHODS: Trial characteristics were extracted from eligible trials identified through two systematic literature searches. Multivariable meta-regression was used to investigate trial characteristics associated with effectiveness estimated using odds ratios. Meta-analysis was used to investigate pooled effectiveness. RESULTS: We identified 201 eligible trials. Compared with China, trials from the USA/Canada (ratio of odds ratio, 1.89; 95% confidence interval, 1.45-2.45) and Europe/Australia/New Zealand (1.67; 1.29-2.18) had an 89% and 67% higher odds ratio, respectively, suggesting reduced effectiveness. The effectiveness was enhanced when the incidence of postoperative delirium increased (0.85; 0.79-0.92, per 10% increase). Trials with concerns related to deviations from intended interventions reported increased effectiveness compared with those at low risk (0.69; 0.53-0.90). Compared with usual care, certain interventions appeared to have reduced the incidence of postoperative delirium in low-risk trials with low-to-moderate certainty of evidence. However, these findings should be considered inconclusive because of challenges in grouping heterogeneous interventions, the limited number of eligible trials, the prevalence of small-scale studies, and potential publication bias. CONCLUSIONS: The effectiveness of postoperative delirium trials varied based on the region of trial origin, the incidence of delirium, and the risk of bias. The limitations caution against drawing definitive conclusions from different bodies of evidence. These findings highlight the imperative need to improve the quality of research on a global scale. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023413984).

The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aß1-42 oligomers through AMPK/mTOR pathway.

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

Genetic diversity and prevalence of emerging Rickettsiales in Yunnan Province: a large-scale study.

BACKGROUND: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. METHODS: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. RESULTS: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. CONCLUSIONS: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China.

Combined genome and transcriptome provides insight into the genetic evolution of an edible halophyte Suaeda salsa adaptation to high salinity.

Suaeda salsa L. is a typical halophyte with high value as a vegetable. Here, we report a 447.98 Mb, chromosomal-level genome of S. salsa, assembled into nine pseudomolecules (contig N50 = 1.36 Mb) and annotated with 27,927 annotated protein-coding genes. Most of the assembled S. salsa genome, 58.03%, consists of transposable elements. Some gene families including HKT1, NHX, SOS and CASP related to salt resistance were significantly amplified. We also observed expansion of genes encoding protein that bind the trace elements Zn, Fe, Cu and Mn, and genes related to flavonoid and α-linolenic acid metabolism. Many expanded genes were significantly up-regulated under salinity, which might have contributed to the acquisition of salt tolerance in S. salsa. Transcriptomic data showed that high salinity markedly up-regulated salt-resistance related genes, compared to low salinity. Abundant metabolic pathways of secondary metabolites including flavonoid, unsaturated fatty acids and selenocompound were enriched, which indicates that the species is a nutrient-rich vegetable. Particularly worth mentioning is that there was no significant difference in the numbers of cis-elements in the promoters of salt-related and randomly selected genes in S. salsa when compared with Arabidopsis thaliana, which may affirm that plant salt tolerance is a quantitative rather than a qualitative trait in terms of promoter evolution. Our findings provide deep insight into the adaptation of halophytes to salinity from a genetic evolution perspective.

The novel KIR2DL3*037 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

The novel KIR2DL3*037 allele differs from the closest allele KIR2DL3*00101 by a single missense mutation.

Genome-Wide Identification and Expression Analysis of the YTH Domain-Containing RNA-Binding Protein Family in Cinnamomum camphora.

N6-methyladenosine (m6A) is one of the most abundant chemical modifications on mRNA in eukaryotes. RNA-binding proteins containing the YT521-B (YTH) domain play crucial roles in post-transcriptional regulation of plant growth, development, and stress response by reading the m6A mark. However, the YTH domain-containing RNA-binding protein family has not been studied in a valuable and medicinal tree such as Cinnamomum camphora (C. camphora) yet. In this study, we identified 10 YTH genes in C. camphora, located on eight out of 12 chromosomes. Phylogenetic analysis revealed that these genes can be classified into two major classes, YTHDF (CcDF) and YTHDC (CcDC). Closely related CcYTHs within the same class exhibited a similar distribution of conserved motifs and domain organization, suggesting functional similarities among these closely related CcYTHs. All CcYTH proteins possessed a highly conserved YTH domain, with CcDC1A containing an additional CCCH domain. The liquid-liquid phase separation (LLPS) predictions indicate that CcDC1A, CcDF1A, CcDF1C, CcDF3C, CcDF4C, and CcDF5C may undergo phase transitions. Quantitative expression analysis revealed that tissue-specific expression was observed fo CcYTHs. Notably, there were two genes, CcDF1A and CcDF5C; both exhibited significantly higher expression levels in various tissues than other genes, indicating that the m6A-YTH regulatory network in C. camphora might be quite distinct from that in most plants such as Arabidopsis thaliana (A. thaliana) with only one abundant YTH protein. According to the analysis of the up-stream cis-regulatory elements of these YTH genes, these genes could be closely related to stress, hormones, and development. The following stress response experiments further verified that their expression levels indeed changed under both PEG and NaCl treatments. These findings not only provide a foundation for future functional analysis of CcYTHs in C. camphora, but also provide insights into the functions of epigenetic mark m6A in forest trees.

Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

Research on identification method of peanut pests and diseases based on lightweight LSCDNet model.

Timely and accurate identification of peanut pests and diseases, coupled with effective countermeasures, are pivotal for ensuring high-quality and efficient peanut production. Despite the prevalence of pests and diseases in peanut cultivation, challenges such as minute disease spots, the elusive nature of pests, and intricate environmental conditions often lead to diminished identification accuracy and efficiency. Moreover, continuous monitoring of peanut health in real-world agricultural settings demands solutions that are computationally efficient. Traditional deep learning models often require substantial computational resources, limiting their practical applicability. In response to these challenges, we introduce LSCDNet (Lightweight Sandglass and Coordinate Attention Network), a streamlined model derived from DenseNet. LSCDNet preserves only the transition layers to reduce feature map dimensionality, simplifying the model's complexity. The inclusion of a sandglass block bolsters features extraction capabilities, mitigating potential information loss due to dimensionality reduction. Additionally, the incorporation of coordinate attention addresses issues related to positional information loss during feature extraction. Experimental results showcase that LSCDNet achieved impressive metrics with an accuracy, precision, recall, and F1 score of 96.67%, 98.05%, 95.56%, and 96.79%, respectively, while maintaining a compact parameter count of merely 0.59M. When compared to established models such as MobileNetV1, MobileNetV2, NASNetMobile, DenseNet-121, InceptionV3, and Xception, LSCDNet outperformed with accuracy gains of 2.65%, 4.87%, 8.71%, 5.04%, 6.32%, and 8.2% respectively, accompanied by substantially fewer parameters. Lastly, we deployed the LSCDNet model on Raspberry Pi for practical testing and application, achieving an average recognition accuracy of 85.36%, thereby meeting real-world operational requirements.

Perilipin1 inhibits Nosema bombycis proliferation by promoting Domeless- and Hop-mediated JAK-STAT pathway activation in Bombyx mori.

Lipid droplets (LDs) are dynamic organelles that participate in the regulation of lipid metabolism and cellular homeostasis inside of cells. LD-associated proteins, also known as perilipins (PLINs), are a family of proteins found on the surface of LDs that regulate lipid metabolism, immunity, and other functions. In silkworms, pébrine disease caused by infection by the microsporidian Nosema bombycis (Nb) is a severe threat to the sericultural industry. Although we found that Nb relies on lipids from silkworms to facilitate its proliferation, the relationship between PLINs and Nb proliferation remains unknown. Here, we found Nb infection caused the accumulation of LDs in the fat bodies of silkworm larvae. The characterized perilipin1 gene (plin1) promotes the accumulation of intracellular LDs and is involved in Nb proliferation. plin1 is similar to perilipin1 in humans and is conserved in all insects. The expression of plin1 was mostly enriched in the fat body rather than in other tissues. Knockdown of plin1 enhanced Nb proliferation, whereas overexpression of plin1 inhibited its proliferation. Furthermore, we confirmed that plin1 increased the expression of the Domeless and Hop in the JAK-STAT immune pathway and inhibited Nb proliferation. Taken together, our current findings demonstrate that plin1 inhibits Nb proliferation by promoting the JAK-STAT pathway through increased expression of Domeless and Hop. This study provides new insights into the complicated connections among microsporidia pathogens, LD surface proteins, and insect immunity.IMPORTANCELipid droplets (LDs) are lipid storage sites in cells and are present in almost all animals. Many studies have found that LDs may play a role in host resistance to pathogens and are closely related to innate immunity. The present study found that a surface protein of insect lipid droplets could not only regulate the morphological changes of lipid droplets but also inhibit the proliferation of a microsporidian pathogen Nosema bombycis (Nb) by activating the JAK-STAT signaling pathway. This is the first discovery of the relationship between microsporidian pathogen and insect lipid surface protein perilipin and insect immunity.

Systematic investigation of the Borrelia miyamotoi spirochetes in ticks, wildlife and domestic animal hosts in Yunnan province, Southwest China.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Bone alteration and esthetics associated with implant-supported prostheses in the anterior maxilla under different implant placement timing: A retrospective clinical study of 1 to 3 years.

STATEMENT OF PROBLEM: Different factors influence alterations in facial bone thickness and esthetic outcomes after implant placement. Whether the timing of implant placement influences alterations in the bone dimensional and esthetic outcomes is unclear. PURPOSE: The purpose of this retrospective clinical study was to assess the influence of the timing of implant placement on alveolar bone alterations and esthetic outcome. MATERIAL AND METHODS: Data were collected from 40 patients who had received guided bone regeneration (GBR) performed simultaneously with immediate, early, or delayed single-tooth implant placement in the anterior maxilla. Facial and palatal horizontal bone thicknesses (FHBT, PHBT) and vertical bone level (FVBL, PVBL) immediately after surgery (T0), at 6 months after implant placement (T1), and at 1 to 3 years follow-up (T2) were measured, and the changes calculated. The pink esthetic score (PES) and white esthetic score (WES) were evaluated at the 1- to 3-year follow-up. The Kruskal-Wallis followed by the Dunn t test was applied to evaluate bone alteration among groups, and the Bonferroni method was used for adjusting multiple comparisons. The 1-way ANOVA test was used to determine any significance in the esthetic outcome in the 3 groups (α=.05). RESULTS: The reduction in the FHBT0 of the immediate, early, and delayed implant placement group (T2-T0) was -1.17 (-1.70, -0.61) mm, -1.53 (-1.69, -0.49) mm, and -1.47 (-2.30, -0.20) mm, respectively. The FHBT around the implant apices remained basically stable. No obvious changes in the PHBT around the implants of the immediate and delayed implant placement group were noted. The FVBL significantly decreased in each group during the follow-up period (-1.34 (01.88, -0.56) mm, immediate; -2.88 (-3.79, -1.07) mm, early; -1.26 (-2.52, -0.48) mm, delayed). The PVBL change in the early implant placement group (-2.18 (-3.26, -0.86) mm) was more significant than that in the immediate (-0.55 (-2.10, -0.17) mm) and delayed (-0.51 (-1.29, 0.02) mm) implantation groups (P =.013). The mean ±standard deviation PES/WES score of the immediate (15.6 ±1.84) and early (15.00 ±1.13) implant placement groups was higher than that of the delayed implant placement group (13.92 ±2.10) without significant difference. CONCLUSIONS: Similar bone changes and esthetic outcomes were found around implants of the immediate, early, and delayed implant placement groups.

[Modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry for detection of cyclopiazonic acid in feeds].

Mycotoxins are toxic secondary metabolites produced by fungal species that can cause acute, subacute, and chronic toxicity in humans and animals. Thus, these toxins pose a significant threat to health and safety. Owing to the lack of effective antimold measures in the agricultural industry, feed ingredients such as corn, peanuts, wheat, barley, millet, nuts, oily feed, forage, and their byproducts are prone to mold and mycotoxin contamination, which can affect animal production, product quality, and safety. Cyclopiazonic acid (CPA), which is mainly biosynthesized from mevalonate, tryptophan, and diacetate units, is a myotoxic secondary metabolite produced by Penicillium and Aspergillus fungi. CPA is widely present as a copollutant with aflatoxins in various crops. Compared with some common mycotoxins such as aflatoxins, fumonisins, ochratoxins, zearalenones, and their metabolites, CPA has not been well investigated. In the United States, a survey showed that 51% of corn and 90% of peanut samples contained CPA, with a maximum level of 2.9 mg/kg. In Europe, CPA was found in Penicillium-contaminated cheeses as high as 4.0 mg/kg. Some studies have shown that CPA can cause irreversible damage to organs such as the liver and spleen in mice. Therefore, the establishment of a rapid and efficient analytical method for CPA is of great significance for the risk assessment of CPA in feeds, the development of standard limits, and the protection of feed product quality and safety. The QuEChERS method, a sample pretreatment method that is fast, simple, cheap, effective, and safe, is widely used in the analysis of pesticide residues in food. In this study, a modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine CPA levels in feeds. The chromatographic separation and MS detection of CPA as well as the key factors affecting the extraction efficiency of CPA, including the type of extraction solvent, type of inorganic salt, and type and dosage of adsorbent, were optimized in detail. During the optimization of the chromatographic-separation step, the acid and salt concentrations of the mobile phase affected the separation and detection of CPA. During the optimization of the QuEChERS method, the addition of a certain amount of acetic acid improved the extraction efficiency of CPA because of its acidic nature; in addition, GCB and PSA significantly adsorbed CPA from the feed extract. Under optimal conditions, the CPA in the feed sample (1.0 g) was extracted with 2 mL of water and 4 mL of acetonitrile (ACN) containing 0.5% acetic acid. After salting out with 0.4 g of NaCl and 1.6 g of MgSO4, 1 mL of the ACN supernatant was purified by dispersive solid-phase extraction using 150 mg of MgSO4 and 50 mg of C18 and analyzed by UPLC-MS/MS. The sample was separated on a Waters HSS T3 column (100 mm×2.1 mm, 1.8 µm) using 2 mmol/L ammonium acetate aqueous solution with 0.5% formic acid and ACN as the mobile phases and then analyzed by positive electrospray ionization in multiple reaction monitoring mode. CPA exhibited good linearity in the range of 2-200 ng/mL, with a high correlation coefficient (r=0.9995). The limits of detection and quantification of CPA, which were calculated as 3 and 10 times the signal-to-noise ratio, respectively, were 0.6 and 2.0 µg/kg, respectively. The average recoveries in feed samples spiked with 10, 100, and 500 µg/kg CPA ranged from 70.1% to 78.5%, with an intra-day precision of less than 5.8% and an inter-day precision of less than 7.2%, indicating the good accuracy and precision of the proposed method. Finally, the modified QuEChERS-UPLC-MS/MS method was applied to the analysis of CPA in 10 feed samples obtained from Wuhan market. The analysis results indicated that the developed method has good applicability for CPA analysis in feed samples. In summary, an improved QuEChERS method was applied to the extraction and purification of CPA from feeds for the first time; this method provides a suitable analytical method for the risk monitoring, assessment, and standard-limit setting of CPA in feed samples.

Body mass index, waist circumference, and mortality in subjects older than 80 years: a Mendelian randomization study.

BACKGROUND AND AIMS: Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. METHODS: A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS: During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. CONCLUSIONS: Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.

Genome-Wide Identification and Expression Analysis of YTH Gene Family for Abiotic Stress Regulation in Camellia chekiangoleosa.

N6-methyladenosine (m6A) is essential for RNA metabolism in cells. The YTH domain, conserved in the kingdom of Eukaryotes, acts as an m6A reader that binds m6A-containing RNA. In plants, the YTH domain is involved in plant hormone signaling, stress response regulation, RNA stability, translation, and differentiation. However, little is known about the YTH genes in tea-oil tree, which can produce edible oil with high nutritional value. This study aims to identify and characterize the YTH domains within the tea-oil tree (Camellia chekiangoleosa Hu) genome to predict their potential role in development and stress regulation. In this study, 10 members of the YTH family containing the YTH domain named CchYTH1-10 were identified from C. chekiangoleosa. Through analysis of their physical and chemical properties and prediction of subcellular localization, it is known that most family members are located in the nucleus and may have liquid-liquid phase separation. Analysis of cis-acting elements in the CchYTH promoter region revealed that these genes could be closely related to abiotic stress and hormones. The results of expression profiling show that the CchYTH genes were differentially expressed in different tissues, and their expression levels change under drought stress. Overall, these findings could provide a foundation for future research regarding CchYTHs in C. chekiangoleosa and enrich the world in terms of epigenetic mark m6A in forest trees.

[Clinical Characteristics of CD4-CD56+ Blastic Plasmacytoid Dendritic Cell Neoplasm].

OBJECTIVE: To explore the clinical manifestations, pathological features, immunophenotype, as well as diagnosis, treatment and prognosis of patients with CD4-CD56+ blastic plasmacytoid dendritic cell neoplasm (BPDCN), in order to further understand the rare disease. METHODS: The clinical data, laboratory examinations and treatment regimens of two patients with CD4-CD56+ BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed. RESULTS: The two patients were both elderly males with tumor involved in skin, bone marrow, lymph nodes, etc. Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive, while CD4, CD34, TdT, CD3, CD20, MPO and EBER were negative. Flow cytometry of bone marrow demonstrated that CD56, CD123, and CD304 were all positive, while specific immune markers of myeloid and lymphoid were negative. Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens, but prone to rapid relapse. The overall survival of both patients was 36 months and 4 months, respectively. CONCLUSION: CD4-CD56+ BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis. Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.

Circulating miR-30e-3p induces disruption of neurite development in SH-SY5Y cells by targeting ABI1, a novel biomarker for schizophrenia.

Schizophrenia (SCZ) represents a set of enduring mental illnesses whose underlying etiology remains elusive, posing a significant challenge to public health. Previous studies have shown that the neurodevelopmental process involving small molecules such as miRNA and mRNA is one of the etiological hypotheses of SCZ. We identified and verified that miR-30e-3p and ABI1 can be used as biomarkers in peripheral blood transcriptome sequencing data of patients with SCZ, and confirmed the regulatory relationship between them. To further explore their involvement, we employed retinoic acid (RA)-treated SH-SY5Y differentiated cells as a model system. Our findings indicate that in RA-induced SH-SY5Y cells, ABI1 expression is up-regulated, while miR-30e-3p expression is down-regulated. Functionally, both miR-30e-3p down-regulation and ABI1 up-regulation promote apoptosis and inhibit the proliferation of SH-SY5Y cells. Subsequently, the immunofluorescence assay detected the expression location and abundance of the neuron-specific protein ß-tubulinIII. The expression levels of neuronal marker genes MAPT, TUBB3 and SYP were detected by RT-qPCR. We observed that these changes of miR-30e-3p and ABI1 inhibit the neurite growth of SH-SY5Y cells. Rescue experiments further support that ABI1 silencing can correct miR-30e-3p down-regulation-induced SH-SY5Y neurodevelopmental defects. Collectively, our results establish that miR-30e-3p's regulation of neurite development in SH-SY5Y cells is mediated through ABI1, highlighting a potential mechanism in SCZ pathogenesis.

CLEC4E upregulation in gastric cancer: A potential therapeutic target correlating with tumor-associated macrophages.

Background: CLEC4E has been reported to promote lung cancer progression. Tumor-associated macrophages (TAMs) play an important role in tumorigenesis. Whether the expression of CLEC4E in TAMs is associated with gastric carcinogenesis remains unclear. Methods: The TIMER, UALCAN, UCSC Xena, and KM plotter databases are used to examine the expression of CLEC4E and its prognostic significance in gastric cancer (GC). Additionally, GO, KEGG, and GSEA analysis were conducted, and single-cell RNA-seq (scRNA-seq) datasets were utilized. The Coremine medical database was used to predict therapeutic drugs, and molecular docking was performed. Human GC samples were obtained, and co-culture models were constructed to evaluate the effects of CLEC4E in TAMs on tumor growth, migration, and invasion in vitro. Results: CLEC4E was significantly upregulated in GC, and high CLEC4E expression was associated with poor prognosis. Western blotting and immunostaining showed increased protein levels of CLEC4E in GC. GO, KEGG, and GSEA results indicated that CLEC4E is involved in immune response. Immune infiltration analysis demonstrated that CLEC4E expression positively correlated with multiple immune cell types. scRNA-seq analyses revealed that CLEC4E was predominantly expressed in myeloid cells specifically TAMs, in GC. In vitro experiments confirmed that MFC induced CLEC4E expression in TAMs to mediate tumor progression. Specifically targeting CLEC4E by si-CLEC4E or stigmasterol inhibited cancer cell migration and invasion. Conclusion: CLEC4E is a potential prognostic biomarker and new therapeutic target for GC that can be specifically targeted by stigmasterol.

Engineered E. coli for D-pantothenic acid production with an acetolactate isomeroreductase mutant.

D-Pantothenic acid, as a momentous vitamin, is extensively applied to feed, medicine, cosmetics and other fields. However, there are still limitations to produce D-pantothenic acid by microbial fermentation at present. In this paper, we constructed a recombinant strain for D-pantothenic acid production by blocking the organic acid pathway, boosting pyruvate biosynthesis, relieving feedback inhibition of acetolactate synthase, improving glucose intake capacity, and modifying essential genes in the metabolic pathway. In addition, a new acetolactate isomeroreductase mutant V412A origin from Escherichia coli (EcAHAIR) encoded by ilvC was obtained to explore its substrate promiscuity. Compared with the wild type, the variant EcAHAIR-V412A has reduced steric hindrance and enhanced intermolecular forces, resulting in a high affinity for 2-acetolactate. Eventually, the fermentation production of the final strain DPAN19/trc-ilvCV412A reached 4.65 g/L, increased by 192.5% compared with strain DPA8 in shake flask cultivation and produced 62.82 g/L D-pantothenic acid in a 5 L bioreactor. The metabolic engineering strategies and enzyme modification approaches described in this paper provide a particular perspective for the bio-manufacturing of D-pantothenic acid, branched-chain amino acids and its derivates.

Natural products for the treatment of chemotherapy-related cognitive impairment and prospects of nose-to-brain drug delivery.

Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI.