Epidemiology of 369 diseases and injuries attributable to 84 risk factors: 1990-2019 with 2040 projection.

The global burden of diseases and injuries poses complex and pressing challenges. This study analyzed 369 diseases and injuries attributed to 84 risk factors globally from 1990 to 2019, projecting trends to 2040. In 2019, global risks caused 35 million deaths. Non-communicable diseases were responsible for 8.2 million deaths, primarily from air pollution (5.5 million). Cardiovascular disease from air pollution had a high age-standardized disability-adjusted life year rate (1,073.40). Communicable, maternal, neonatal, and nutritional diseases caused 1.4 million deaths, mainly due to unsafe water and sanitation. Occupational risks resulted in 184,269 transport-related deaths. Behavioral risks caused 21.6 million deaths, with dietary factors causing 6.9 million cardiovascular deaths. Diabetes linked to sugar-sweetened beverages showed significant growth (1990-2019). Metabolic risks led to 18.6 million deaths. Projections to 2040 indicated persistent challenges, emphasizing the urgent need for targeted interventions and policies to alleviate the global burden of diseases and injuries.

(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

Human Adipose Tissue-Derived Stromal Cells Ameliorate Adriamycin-Induced Nephropathy by Promoting Angiogenesis.

This study is to investigate the therapeutical effect and mechanisms of human-derived adipose mesenchymal stem cells (ADSC) in relieving adriamycin (ADR)-induced nephropathy (AN). SD rats were separated into normal group, ADR group, ADR+Losartan group (20 mg/kg), and ADR + ADSC group. AN rats were induced by intravenous injection with adriamycin (8 mg/kg), and 4 d later, ADSC (2 × 105 cells/mouse) were administrated twice with 2 weeks interval time (i.v.). The rats were euthanized after the 6 weeks' treatment. Biochemical indicators reflecting renal injury, such as blood urea nitrogen (BUN), neutrophil gelatinase alpha (NGAL), serum creatinine (Scr), inflammation, oxidative stress, and pro-fibrosis molecules, were evaluated. Results demonstrated that we obtained high qualified ADSCs for treatment determined by flow cytometry, and ADSCs treatment significantly ameliorated renal injuries in DN rats by decreasing BUN, Scr and NGAL in peripheral blood, as well as renal histopathological injuries, especially protecting the integrity of podocytes by immunofluorescence. Furthermore, ADSCs treatment also remarkably reduced the renal inflammation, oxidative stress, and fibrosis in DN rats. Preliminary mechanism study suggested that the ADSCs treatment significantly increased renal neovascularization via enhancing proangiogenic VEGF production. Pharmacodynamics study using in vivo imaging confirmed that ADSCs via intravenous injection could accumulate into the kidneys and be alive at least 2 weeks. In a conclusion, ADSC can significantly alleviate ADR-induced nephropathy, and mainly through reducing oxidative stress, inflammation and fibrosis, as well as enhancing VEGF production.

Comprehensive identification and risk assessment of regulated and emerging mycotoxins in infant foods and related raw materials and risk management advice: A case study of an infant food company in China.

This study evaluated muti-mycotoxins in 199 samples including processed infant foods and raw materials collected randomly from an infant food company and assessed their role in dietary exposure in infants and young children via probabilistic risk assessment. Approximately 79.6 % (74/93) of the processed infant foods and 65.1 % (69/106) of the raw materials were contaminated by mycotoxins, with a mean occurrence level of 3.66-321.8 µg/kg. Deoxynivalenol (DON) and tenuazonic acid (TeA) were the more prevalent mycotoxins detected, based on their higher frequencies and levels across samples. Co-occurrence of more than two mycotoxins was detected in 61.3 % (57/93) of the processed infant foods and 53.8 % (57/106) of the raw materials. Wheat flour and derived products (e.g., infant noodles and infant biscuits) were contaminated with higher contamination levels and a greater variety of mycotoxins than other samples (e.g., infant cereal and rice grains). The estimated daily exposure to OTA, DON, ZEN, and TEN was lower than the corresponding reference health-based guidance values, indicating acceptable health risks. However, the estimated dietary exposure to alternariol monomethyl ether (AME), alternariol (AOH), and tenuazonic acid (TeA) exceeded the corresponding thresholds of toxicological concern values, indicating potential dietary intake risks. Among the various samples, cereals and cereal-based infant foods emerged as the primary contributors to mycotoxin exposure. Further research is advised to address the uncertainties surrounding the toxicity associated with emerging Alternaria mycotoxins and to conduct cumulative risk assessments concerning multiple mycotoxin exposure in infants and young children.

Exacerbated lung inflammation in offspring with high maternal antibody levels following secondary RSV exposure.

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.

Enhanced Osteosarcoma Immunotherapy via CaCO3 Nanoparticles: Remodelling Tumour Acidic and Immune Microenvironment for Photodynamic Therapy.

Osteosarcoma (OS) is a "cold" tumour enriched in noninflammatory M2 phenotype tumour-associated macrophages (TAMs), which limits the efficacy of immunotherapy. The acidic tumour microenvironment (TME), generated by factors such as excess hydrogen (H+) ions and high lactate levels, activates immunosuppressive cells (e.g., M2 phenotype TAMs), further promoting a suppressive tumour immune microenvironment (TIME). Therefore, a multitarget synergistic combination strategy that neutralizes the acidic TME and reprograms TAMs can be beneficial for OS therapy. Here, a calcium carbonate (CaCO3)/polydopamine (PDA)-based nanosystem (A-NPs@(SHK+Ce6)) was developed for the targeted codelivery of the photosensitizer Ce6 and shikonin (SHK) to OS tumours via the bone-targeting ability of alendronate sodium (ALN). CaCO3 nanoparticles were used to neutralize H+ ions and alleviate the suppressive TIME, and the loaded SHK not only synergized with photodynamic therapy (PDT) by promoting reactive oxygen species (ROS) generation and enhancing immunogenic cell death (ICD) but also inhibited lactate production, further reversing the acidic TME and repolarizing TAMs to consequently lead to enhanced PDT-induced tumour suppression and comprehensive beneficial effects on antitumour immune responses, including the promotion of CD8+ T-cell infiltration and regulatory T-cell (Treg) suppression. Importantly, A-NPs@(SHK+Ce6), in combination with programmed cell death protein 1 (PD-1) checkpoint blockade, showed a remarkable ability to eliminate distant tumours and promote long-term immune memory function to protect against rechallenged tumours. This work presents a novel multiple-component combination strategy that coregulates the acidic TME and TAM polarization to reprogram the TIME. This article is protected by copyright. All rights reserved.

Recurrent neural network for predicting absence of heterozygosity from low pass WGS with ultra-low depth.

BACKGROUND: The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). RESULTS: Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. CONCLUSIONS: Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

Anti-inflammatory lindenane sesquiterpenoid dimers from the roots of Chloranthus holostegius var. trichoneurus.

Two new lindenane-type sesquiterpenoid dimers, chlotrichenes C and D (1 and 2) together with five known lindenane-type sesquiterpenoid dimers (3-7) were isolated from the roots of Chloranthus holostegius var. trichoneurus, a famous natural medicine named as "Sikuaiwa" for subduing swellings and relieving pain. The structures including absolute configuration were elucidated by their 1D and 2D NMR, HRESIMS, and ECD data. Compounds 1 and 2 were classical [4 + 2] lindenane-type sesquiterpenoid dimers that differed from known analogs in oxidation profile, side chain profile, and double bond position. The new isolates and compound 3 exhibited significant inhibitory activity on IL-1ß production (IC50: 1-15 µM) in LPS-induced THP-1 cells and other compounds exhibited inhibitory activity on NO production in LPS-induced RAW 264.7 cells (IC50: 24-33 µM).

Co-production of 1,3-propanediol and phage phiKpS2 from the glycerol fermentation by Klebsiella pneumoniae.

As an alternative to antibiotics in response to antimicrobial-resistant infections, bacteriophages (phages) are garnering renewed interest in recent years. However, the massive preparation of phage is restricted using traditional pathogens as host cells, which incurs additional costs and contamination. In this study, an opportunistic pathogen, Klebsiella pneumoniae used to convert glycerol to 1,3-propanediol (1,3-PDO), was reused to prepare phage after fermentation. The phage infection showed that the fed-batch fermentation broth containing 71.6 g/L 1,3-PDO can be directly used for preparation of phage with a titer of 1 × 108 pfu/mL. Then, the two-step salting-out extraction was adopted to remove most impurities, e.g. acetic acid (93.5%), ethanol (91.5%) and cells (99.4%) at the first step, and obtain 1,3-PDO (56.6%) in the top phase as well as phage (97.4%) in the middle phase at the second step. This integrated process provides a cheap and environment-friendly manner for coproduction of 1,3-PDO and phage.

Role of ICAM-1 in triple-negative breast cancer.

Intercellular adhesion molecule-1 (ICAM-1) is related to the occurrence and development of a variety of tumors. However, the role of ICAM-1 in the regulation of growth, metastasis, and clinical prognosis of the specific molecular subtypes of breast cancer, triple-negative breast cancer (TNBC), remains to be elucidated. This study explored the role of ICAM-1 in breast cancer and its triple-negative subtypes by systematic bioinformatics methods. The results showed that the expression of ICAM-1 in breast cancer tissues was significantly higher than that in normal tissues, especially in TNBC subtypes. In breast cancer, ICAM-1 mainly activates pathways related to apoptosis and epithelial-mesenchymal transition, while its overexpression in TNBC is associated with inflammatory response, apoptosis, and other processes. TNBC patients displaying higher ICAM-1 expression demonstrate enhanced responses to immunotherapy. High ICAM-1 expression is sensitive to drugs targeting tumor cell proliferation, apoptosis, and angiogenesis. In conclusion, breast cancer is characterized by significantly high expression of ICAM-1, with TNBC subtypes expressing ICAM-1 at much higher levels than other subtypes. The diagnosis, prognosis, development, distant metastases, and immunotherapy of TNBC are correlated with high expression of ICAM-1. This research provides available data for the further study of the diagnosis and treatment of TNBC.

Quantitative for photochemical loss of volatile organic compounds upon ozone formation chemistry at an industrial City (Zibo) in North China Plain.

Volatile organic compounds (VOCs) are consumed by photochemical reactions during transport, leading to inaccuracies in estimating the local ozone (O3) formation mechanism and its subsequent strategy for O3 attainment. To comprehensively quantify the deviations in O3 formation mechanism by consumed VOCs (C-VOCs), a 5-month field campaign was conducted in a typical industrial city in Northern China over incorporating a 0-D box model (implemented with MCMv3.3.1). The averaged C-VOCs concentration was 6.8 ppbv during entire period, and Alkenes accounted for 62% dominantly. Without considering C-VOCs, the relative incremental reactivity (RIR) of anthropogenic VOCs (AVOC, overestimated by 68%-75%) and NOx (underestimated by 137%-527%) demonstrated deviations at multiple scenarios, and the RIR deviations for precursors in High-O3-periods (HOP) were lower than Low-O3-periods (LOP). The RIR deviations from individual species involved C-VOCs calculation did not impact the identification for the high-ranking-RIR AVOC species but non-negligible. Monthly comparisons showed that higher C-VOCs concentrations would lead to higher RIR deviations. The daily maximum of net Ox production rate (P(Ox)) and the regional transport Ox (Trans(Ox)) without C-VOCs were underestimated by 56%-194% and 81%-243%, respectively. After considering C-VOCs, the contribution of HO2+NO for Ox gross production (G(Ox)) decreased by 7% (LOP) and 7% (HOP), but OH+NO2 for Ox destruction (D(Ox)) decreased by 16% (LOP) and 23% (HOP), and alkenes+O3 increased for D(Ox) by 12% (LOP) and 22% (HOP). This implies that VOCs-NOx-O3 sensitivity was deviated between with/without C-VOCs, and severe O3 pollution rendered deviations in O3 formation, especially via NOx-driving chemistry. Based on RIR(NOx)/RIR(AVOC) with/without C-VOCs, the sensitivity regime shifted from VOCs-limited (-0.93) to transition (1.38) at LOP, and from VOCs-limited (0.19) to NOx-limited (3.79) at HOP. Our results reflected that the NOx limitation degree was underestimated without constraint C-VOCs, especially HOP, and provided implication to more precise O3 pollution control strategies.

SARS-CoV-2 Infection Increases High Risk Rate of Down Syndrome Screening Test by Reducing Alpha-Fetoprotein.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a significant global health issue in recent years. Numerous studies indicate that COVID-19 during pregnancy is associated with an increased likelihood of pregnancy complications. Additionally, pregnancy itself is known to elevate the risk of severe SARS-CoV-2 infection. To explore the potential impact of SARS-CoV-2 infection on the probability of Down syndrome in fetuses, we conducted serological testing of Down syndrome markers in pregnant women who had contracted the virus. METHODS: Serological experiments were conducted utilizing a particle chemiluminescence test. The cohort of pregnant women was categorized into three groups: a control group with no infection, a group infected with SARS-CoV-2 Omicron within the first six weeks of gestation, and a group infected beyond the sixth week of gestation. RESULTS: In the group of individuals infected within 6 gestational weeks, the infection resulted in a decrease in alpha-fetoprotein (AFP) levels and a higher positive rate of Down syndrome screening tests (p ˂ 0.05). However, in this study, SARS-CoV-2 infection did not lead to an increase in the occurrence of Down syndrome in the fetus. The positive rate of women infected beyond 6 gestational weeks was slightly higher than the non-infected group (6.2% vs. 5.7%), but these differences were not statistically significant (p > 0.05). Within the group infected beyond 6 gestational weeks, there was, compared to the control group, a decrease in free beta human chorionic gonadotropin (ß-hCG) levels (p < 0.05). CONCLUSIONS: This study presents a novel investigation into the impact of SARS-CoV-2 infection on AFP and ß-hCG levels. It has been observed that pregnant women who contract SARS-CoV-2 may exhibit an increased likelihood of positive results in serum tests conducted for Down syndrome screening. However, it is important to note that the occurrence of Down syndrome in the developing fetus does not appear to be elevated. To validate these findings, additional research involving larger and diverse cohorts is necessary.

Decision analysis of PPP project's parties based on deep consumer participation.

Although PPP(Public-private partnership) mode has been applied for a long time in infrastructural project, the success rate is not very high. The sustainability of PPP projects is still influenced by many factors. In order to examine the evolutionary stable strategies (ESSs) of social capital, government, and paying consumers, a tripartite evolutionary game model is established in this work. In order to further promote consumer participation, it is necessary to make the assumption that customer oversight and review can have an impact on service prices. The results show: i)The strategy choice of consumer depends on the comparison between supervision cost of consumer and price coefficient for consumer to social capital. ii)Consumer supervision can promote the provision of high-quality services by social capital. iii)The difference between high-quality cost and low-quality cost, subsidy coefficient, price coefficient and supervision cost of consumer are critical factors influencing both evolutionary results and trajectories. This paper also puts forward policy implications for the three stakeholders to promote social capital's high-quality strategy so as to maintain the sustainability of PPP projects.

Synthetic analysis of trophic diversity and evolution in Enantiornithes with new insights from Bohaiornithidae.

Enantiornithines were the dominant birds of the Mesozoic, but understanding of their diet is still tenuous. We introduce new data on the enantiornithine family Bohaiornithidae, famous for their large size and powerfully built teeth and claws. In tandem with previously published data, we comment on the breadth of enantiornithine ecology and potential patterns in which it evolved. Body mass, jaw mechanical advantage, finite element analysis of the jaw, and traditional morphometrics of the claws and skull are compared between bohaiornithids and living birds. We find bohaiornithids to be more ecologically diverse than any other enantiornithine family: Bohaiornis and Parabohaiornis are similar to living plant-eating birds; Longusunguis resembles raptorial carnivores; Zhouornis is similar to both fruit-eating birds and generalist feeders; and Shenqiornis and Sulcavis plausibly ate fish, plants, or a mix of both. We predict the ancestral enantiornithine bird to have been a generalist which ate a wide variety of foods. However, more quantitative data from across the enantiornithine tree is needed to refine this prediction. By the Early Cretaceous, enantiornithine birds had diversified into a variety of ecological niches like crown birds after the K-Pg extinction, adding to the evidence that traits unique to crown birds cannot completely explain their ecological success.

The birds living in the world today are only a small part of the larger bird family tree. Around 120 to 65 million years ago, when dinosaurs and other large reptiles roamed the world, the ancestors of modern-day birds were actually rather rare. Instead, another now extinct group of birds called the Enantiornithes (meaning "opposite birds") were the most common birds. Many researchers believe that Enantiornithes may have filled similar roles in ancient ecosystems as living birds do today. For example, some may have hunted other birds or animals, while some may have eaten only plants. Some may have specialized at eating a few specific foods while others may have been 'generalists' that ate many different foods. However, some of the physical features of Enantiornithes set them apart from modern-day birds. For example, unlike living birds, Enantiornithes had teeth and their wings were also constructed very differently. Previous studies suggest that one group of these extinct birds most likely ate insects and another group most likely ate fish, but it remains unclear what variety of foods opposite birds as a whole may have consumed. Miller et al. compared the jaws, claws and various other physical features of fossils from six additional species of opposite birds with the skeletons of modern birds to infer what the diets of these opposite birds may have been. This approach revealed that Enantiornithes may have had a wide variety of different diets. The researchers found that two species probably ate plants, another species most likely ate meat, and another one likely ate a mixture of both. With a large sample across Enantiornithes, Miller et al. were able to predict the diet of their common ancestor. They found the common ancestor to most likely be a 'generalist' eating variety of foods and that some species subsequently evolved to have more specialist diets. Opposite birds probably played many different roles in ecosystems, like living birds do today. Therefore, a better understanding how Enantiornithes evolved may shed light on the factors that have influenced the evolution of modern-day birds. This may aid future conservation efforts to target birds whose descendants may be able to take up the ecological roles of other species that go extinct.

Fever-induced acute sleep terrors in children and adolescents following SARS-CoV-2 infection.

OBJECTIVE: This study aims to provide physicians with insights into the clinical manifestations and outcomes of children and young adolescents experiencing sleep terrors following SARS-CoV-2 infection. METHODS: We enrolled patients who developed new onset sleep terrors after SARS-CoV-2infection fromDecember2022to April 2023 in the Xijing hospital, Xi'an, China. RESULTS: We enrolled six patients who experienced sleep terrors following SARS-CoV-2 infection. Out of these patients, five were children and only one was an adolescent, with a mean age of 9 years. Neuroimaging results were negative for all cases. Sleep terrors occurred during both the active course of COVID-19 illness and the recovery period in all patients. Symptoms included crying or screaming in terror, hyperactivity, inappropriate behavior and periods of mental confusion during sleep. These episodes typically occurred 40 min to 1 h after falling asleep. EEG monitoring confirmed two patients' episodes occurred during non-rapid eye movement (NREM) stage 3 sleep. The duration of sleep terrors ranged from 3mines to30 mines, with each patient experiencing 3-4 to 30-40 instances. Initially, the frequency of episodes was highest at 3-4 times per night, gradually decreasing to once a night, then once a week, until complete disappearance. No medical intervention was required. Clinical follow-up ranged from 6 to 12 months, with spontaneous remission occurring within 1 week to 2 months for different patients. CONCLUSION: SARS-CoV-2 infection may precipitate acute sleep terrors in children and adolescents. The course of these sleep terrors is generally benign, with all patients achieving spontaneous complete remission over time.

Electrochemical Benzylic C(sp3)-H Imidation Enabled by Benzoic Acid Derived Radicals.

We developed an electrochemical approach for benzylic C(sp3)-H imidation by virtue of the in situ generated oxygen-centered radicals (OCRs). The electrochemical imidation provides a complementary approach to giving distinct imide products compared with previous acyloxylation products. This protocol exhibits good site selectivity and broad substrate generality. Moreover, the utility of the OCR-mediated protocol was extended to the electrochemical oxidation of silane, and its robustness was also highlighted by the imidation of complex substrates, which would otherwise be inaccessible for previous approaches. A plausible reaction mechanism was proposed to rationalize the experimental observations.

A lateral flow assay for miRNA-21 based on CRISPR/Cas13a and MnO2 nanosheets-mediated recognition and signal amplification.

The point-of-care testing (POCT) of miRNA has significant application in medical diagnosis, yet presents challenges due to their characteristics of high homology, low abundance, and short length, which hinders the achievement of quick detection with high specificity and sensitivity. In this study, a lateral flow assay based on the CRISPR/Cas13a system and MnO2 nanozyme was developed for highly sensitive detection of microRNA-21 (miR-21). The CRISPR/Cas13a cleavage system exhibits the ability to recognize the specific oligonucleotide sequence, where two-base mismatches significantly impact the cleavage activity of the Cas13a. Upon binding of the target to crRNA, the cleavage activity of Cas13a is activated, resulting in the unlocking of the sequence and initiating strand displacement, thereby enabling signal amplification to produce a new sequence P1. When applying the reaction solution to the lateral flow test strip, P1 mediates the capture of MnO2 nanosheets (MnO2 NSs) on the T zone, which catalyzes the oxidation of the pre-immobilized colorless substrate 3,3',5,5'-tetramethylbenzidine (TMB) on the T zone and generates the blue-green product (ox-TMB). The change in gray value is directly proportional to the concentration of miR-21, allowing for qualitative detection through visual inspection and quantitative measurement using ImageJ software. This method achieves the detection of miR-21 within a rapid 10-min timeframe, and the limit of detection (LOD) is 0.33 pM. With the advantages of high specificity, simplicity, and sensitivity, the lateral flow test strip and the design strategy hold great potential for the early diagnosis of related diseases.

Xylanase Supplement Enhances the Growth Performance of Broiler by Modulating Serum Metabolism, Intestinal Health, Short-Chain Fatty Acid Composition, and Microbiota.

This study aimed to investigate the effects of different levels of xylanase supplementation in a wheat-based diet on growth performance, short-chain fatty acids, intestinal health, microbial composition, and serum metabolism. A total of 1200 male chicks were randomly assigned to four wheat-based diet treatments: Group C (adding 0 mg/kg of xylanase), Group L (adding 50 mg/kg of xylanase), Group M (adding 100 mg/kg of xylanase), and Group H (adding 150 mg/kg of xylanase). The experiment lasted for 56 days. The results indicated that Group H broilers experienced a decreased feed-to-gain ratio throughout the study period. Additionally, dietary supplementation with xylanase led to an increase in the physical barrier, as indicated by increased VH and VH/CD in the gut (p < 0.05). Furthermore, levels of D-lactic acid and endotoxin were reduced. Xylanase supplementation also increased the abundance of Muc-2, ZO-1, and Occludin (p < 0.05). Moreover, xylanase supplementation enhanced the activity of sucrase and maltase in the duodenum (p < 0.05), which may be attributable to the upregulation of the abundance of SI and MGA (p < 0.05). Furthermore, xylanase addition promoted propionic acid produced by specific bacteria, such as Phascolarctobacterium, and influenced the microbial composition to some extent, promoting intestinal health. Additionally, 150 mg/kg of xylanase supplementation increased the amino acid, peptide, and carbohydrate content and upregulated the metabolism of amino acids related to histidine, cysteine, methionine, and other pathways (p < 0.05). These findings suggest adequate xylanase supplementation can enhance nutritional digestibility and absorption, improve growth performance, stimulate endogenous enzyme activity, optimize intestinal morphology and barrier function, and positively influence acid-producing bacteria and amino acid metabolic pathways.

Depressive symptoms, parenting attitude, and violent discipline among caregivers of left-behind children in rural China: a cross-sectional study.

BACKGROUND: The situation of mental health and discipline behaviors of left-behind children's caregivers were not optimistic in rural China. Caregivers' depression might increase the risk of using violent discipline. However, the specific ways in which depressive symptoms impact violent discipline have rarely been explored in rural areas. This study aims to assess the prevalence of violent discipline among left-behind children under 6 years of age in rural China and explore the potential mechanisms of how caregivers' depressive symptoms affect violent discipline. METHODS: We enrolled a total of 396 pairs of left-behind children and their caregivers in our study, which was conducted in 5 counties of Hebei, Henan, Jiangxi, Guizhou, and Sichuan provinces in China. The depressive symptoms of caregivers were measured by using Zung Self-rating Depression Scale (ZSDS) and violent discipline was assessed by the Child Discipline Module of Multiple Indicator Cluster Surveys (MICS). A self-designed questionnaire was utilized to measure caregiver's parenting attitude. Based on the cross-sectional data, controlling for potential confounders, structural equation modeling (SEM) was used to assess the direct and indirect effects of the mediation models by applying the weighted least squares with mean and variance adjusted (WLSMV) estimate. RESULTS: The prevalence of violent discipline, psychological aggression, and physical punishment was 72.7%, 59.3%, and 60.4% respectively of left-behind children under 6 years of age. According to the results of SEM, parenting attitude acted as a suppressor, suppressing the association between caregivers' depressive symptoms and physical punishment/psychological aggression/violent discipline. The caregivers' depressive symptoms positively influenced all the outcome variables by affecting parenting attitudes (p = 0.002, p = 0.013, p = 0.002). CONCLUSIONS: The presence of depressive symptoms in caregivers increases the use of violent discipline through negative parenting attitudes. The mental health status of primary caregivers of left-behind children in rural China needed emphasis and improvement.