Prevalence and determinants of constipation in children in Asia: a systematic review and meta-analysis.

Background: Constipation is prevalent worldwide, significantly increasing healthcare costs and diminishing the quality of life in children affected. Current studies have yielded mixed results regarding the factors associated with constipation, and mainly focusing on patients outside of Asia. Moreover, most of these studies lack focus on the paediatric population. This study aimed to identify the prevalence and associated factors of constipation among children in Asia. Methods: In this systematic review and meta-analysis, we systematically searched PubMed, Scopus, and Cochrane for cohort and cross-sectional studies published from database inception up to October 12, 2022, and continued with manual searching until September 2, 2023. Eligible studies were those that included children in Asia aged 0-18 years old suffering from idiopathic constipation, with prevalence value provided in the English abstract. The analysis included clinical and general population. Children with organic constipation, who had undergone gastrointestinal surgery, or with congenital defects were excluded, as these factors affect the incidence of constipation. Data included in the analysis were extracted from published reports only. The extracted data were pooled using random-effects model to analyse the prevalence of constipation in children in Asia. This study is registered with PROSPERO, CRD42022367122. Findings: Out of 4410 systematically searched studies and 36 manually searched ones, a total of 50 studies were included in the final analysis, encompassing data from 311,660 children residing in Asia. The pooled prevalence of constipation was 12.0% (95% CI 9.3-14.6%, I2 = 99.8%). There was no significant difference in constipation prevalence observed by sex and geographical location. Nonetheless, adolescents and children aged 1-9 years exhibited a significantly higher prevalence constipation compared to infants (p < 0.0001) Additionally, significant differences in constipation rates were observed across various diagnostic methods, population sources, and mental health conditions. Interpretation: Despite the high heterogeneity resulting from varying diagnostic tools or definitions used among studies, our review adds to the literature on constipation among children in Asia. It reveals a notably high prevalence of constipation in this demographic. Diagnostic methods, age, and compromised mental health emerged as significant influencers of constipation among children in Asia, highlighting potential strategies to mitigate constipation prevalence in children in Asia. Funding: The National Science and Technology Council, Taiwan.

Targeting PARP14 with lomitapide suppresses drug resistance through the activation of DRP1-induced mitophagy in multiple myeloma.

Multiple myeloma (MM) is a hematological malignancy that remains incurable, primarily due to the high likelihood of relapse or development of resistance to current treatments. To explore and discover new medications capable of overcoming drug resistance in MM, we conducted cell viability inhibition screens of 1504 FDA-approved drugs. Lomitapide, a cholesterol-lowering agent, was found to exhibit effective inhibition on bortezomib-resistant MM cells in vitro and in vivo. Our data also indicated that lomitapide decreases the permeability of the mitochondrial outer membrane and induces mitochondrial dysfunction in MM cells. Next, lomitapide treatment upregulated DRP1 and PINK1 expression levels, coupled with the mitochondrial translocation of Parkin, leading to MM cell mitophagy. Excessive mitophagy caused mitochondrial damage and dysfunction induced by lomitapide. Meanwhile, PARP14 was identified as a direct target of lomitapide by SPR-HPLC-MS, and we showed that DRP1-induced mitophagy was crucial in the anti-MM activity mediated by PARP14. Furthermore, PARP14 is overexpressed in MM patients, implying that it is a novel therapeutic target in MM. Collectively, our results demonstrate that DRP1-mediated mitophagy induced by PARP14 may be the cause for mitochondrial dysfunction and damage in response to lomitapide treatment.

Tunnel-Oriented VO2 (B) Cathode for High-Rate Aqueous Zinc-Ion Batteries.

Tunnel-type vanadium oxides are promising cathodes for aqueous zinc ion batteries. However, unlike layer-type cathodes with adjustable layer distances, enhancing ion-transport kinetics in tunnels characterized by fixed sizes poses a considerable challenge. This study highlights that the macroscopic arrangement of the electrode crucially determines tunnel orientation, thereby influencing ion transport. By changing the material morphology, the tunnel orientation can be optimized to facilitate rapid ion diffusion. In a proof-of-concept demonstration, it is revealed that (00l) facets-dominated VO2 (B) nanobelts with dispersive morphology (VO2-D) tend to adopt a stacking pattern with directional ion transport along the c-axis on the electrode and guarantee fast ion diffusion. Compared with the aggregated sample (VO2-A) that tends to random arrangement on the electrode with isotropic and slow ion transfer behavior, the electrode featuring dispersive (00l) facets-dominated VO2 (B) nanobelts displays directional and fast ion diffusion behavior, thus exhibits an ultrahigh-rate performance (420.8 and 344.8 mAh g-1 at 0.1 and 10 A g-1, respectively) and long cycling stability (84.3% capacity retention under 5000 cycles at 10 A g-1). The results suggest that simultaneous manipulation of exposed crystal facet and morphology-related electrode arrangement should be promising for boosting the ion-transport kinetics in tunnel-type vanadium oxide cathodes.

CLPs-miR-103a-2-5p inhibits proliferation and promotes cell apoptosis in AML cells by targeting LILRB3 and Nrf2/HO-1 axis, regulating CD8 + T cell response.

BACKGROUND: LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment. METHODS: Potential miRNAs binding to the 3'-untranslated region (3'-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo. RESULTS: LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth. CONCLUSIONS: MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.

Unveiling the role of ferrous ion in driving microalgae granulation from salt-tolerant strains for mariculture wastewater treatment.

Development of microalgal-bacterial granular sludge (MBGS) from saline-adapted microalgae is a promising approach for efficient mariculture wastewater treatment, whereas the elusive mechanisms governing granulation have impeded its widespread adoption. In this study, spherical and regular MBGS were successfully developed from mixed culture of pure Spirulina platensis and Chlorella sp. GY-H4 at 10 mg/L Fe2+ concentration. The addition of Fe2+ was proven to induce the formation of Fe-precipitates which served as nucleation sites for microbial attachment and granulation initiation. Additionally, Fe2+ increased the prevalence of exopolysaccharide-producing cyanobacteria, i.e. Synechocystis and Leptolyngbya, facilitating microbial cell adhesion. Furthermore, it stimulated the secretion of extracellular proteins (particularly tryptophan and aromatic proteins), which acted as structural backbone for the development of spherical granule form microalgal flocs. Lastly, it fostered the accumulation of exogenous heterotrophic functional genera, resulting in the efficient removal of DOC (98 %), PO43--P (98 %) and NH4+-N (87 %). Nevertheless, inadequate Fe2+ hindered microalgal floc transformation into granules, excessive Fe2+ expanded the anaerobic zone within the granules, almost halved protein content in the TB-EPS, and inhibited the functional genes expression, ultimately leading to an irregular granular morphology and diminished nutrient removal. This research provides valuable insights into the mechanisms by which Fe2+ promotes the granulation of salt-tolerant microalgae, offering guidance for the establishment and stable operation of MBGS systems in mariculture wastewater treatment.

Converting Commercial Zn Foils into Single (002)-Textured Zn with Millimeter-Sized Grains for Highly Reversible Aqueous Zinc Batteries.

Rechargeable aqueous zinc batteries are promising but hindered by unfavorable dendrite growth and side reactions on zinc anodes. In this study, we demonstrate a fast melting-solidification approach for effectively converting commercial Zn foils into single (002)-textured Zn featuring millimeter-sized grains. The melting process eliminates initial texture, residual stress, and grain size variations in diverse commercial Zn foils, guaranteeing the uniformity of commercial Zn foils into single (002)-textured Zn. The single (002)-texture ensures large-scale epitaxial and dense Zn deposition, while the reduction in grain boundaries significantly minimizes intergranular reactions. These features enable large grain single (002)-textured Zn shows planar and dense Zn deposition under harsh conditions (100 mA cm-2, 100 mAh cm-2), impressive reversibility in Zn||Zn symmetric cell (3280 h under 1 mA cm-2, 830 h under 10 mAh cm-2), and long cycling stability over 180 h with a high depth of discharge value of 75 %. This study successfully addresses the issue of uncontrollable texture formation in Zn foils following routine annealing treatments with temperatures below the Zn melting point. The findings of this study establish a highly efficient strategy for fabricating highly reversible single (002)-textured Zn anodes.

Using the Conditional Process Analysis Model to Characterize the Evolution of Carbon Structure in Taxodium ascendens Biochar with Varied Pyrolysis Temperature and Holding Time.

Temperature determines biochar structure during pyrolysis. However, differences in holding time and feedstock types may affect this relationship. The conditional process analysis model was used in this paper to investigate the potential to affect this mechanism. The branch and leaf parts of Taxodium ascendens were separately pyrolyzed at 350, 450, 650, and 750 °C, and kept for 0.5, 1, and 2 h at each target temperature. We measured the fixed carbon and ash contents and the elemental composition (C, H, O and N) of the raw materials and their char samples. After plotting a Van Krevelen (VK) diagram to determine the aromatization of chars, the changes in the functional groups were analyzed using Fourier transform infrared (FTIR), Raman, and X-ray photoelectron spectroscopy (XPS). The results revealed that pyrolysis at temperatures between 450 and 750 °C accounted for the aromatization of biochar because the atomic H/C ratio of branch-based chars (BC) decreased from 0.53-0.59 to 0.15-0.18, and the ratio of leaf-based chars (LC) decreased from 0.56-0.68 to 0.20-0.22; the atomic O/C ratio of BC decreased from 0.22-0.27 to 0.08-0.11, while that of LC decreased from 0.26-0.28 to 0.18-0.21. Moreover, the average contents of N (1.89%) and ash (13%) in LC were evidently greater than that in BC (N:0.62%; Ash: 4%). Therefore, BC was superior to LC in terms of the stability of biochar. In addition, the increasing ID/IG and ID/I(DR+GL) ratios in BC and LC indicated an increasing amount of the amorphous aromatic carbon structure with medium-sized (2~6 rings) fused benzene rings. According to the CPA analysis, an extension of the holding time significantly enhanced the increase in aromatic structures of LC with temperature. But this extension slightly reduced the growth in aromatic structures of BC. All indicate that holding time and feedstock types (branch or leaf feedstock) could significantly affect the variation in biochar aromatic structure with respect to temperature.

Deep learning in water protection of resources, environment, and ecology: achievement and challenges.

The breathtaking economic development put a heavy toll on ecology, especially on water pollution. Efficient water resource management has a long-term influence on the sustainable development of the economy and society. Economic development and ecology preservation are tangled together, and the growth of one is not possible without the other. Deep learning (DL) is ubiquitous in autonomous driving, medical imaging, speech recognition, etc. The spectacular success of deep learning comes from its power of richer representation of data. In view of the bright prospects of DL, this review comprehensively focuses on the development of DL applications in water resources management, water environment protection, and water ecology. First, the concept and modeling steps of DL are briefly introduced, including data preparation, algorithm selection, and model evaluation. Finally, the advantages and disadvantages of commonly used algorithms are analyzed according to their structures and mechanisms, and recommendations on the selection of DL algorithms for different studies, as well as prospects for the application and development of DL in water science are proposed. This review provides references for solving a wider range of water-related problems and brings further insights into the intelligent development of water science.

The function of sphingolipids in different pathogenesis of Alzheimer's disease: A comprehensive review.

Sphingolipids (SPLs) represent a highly diverse and structurally complex lipid class. The discussion of SPL metabolism-related issues is of importance in understanding the neuropathological progression of Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular deposits of the amyloid ß-peptide (Aß) and intraneuronal aggregates of the microtubule-associated protein tau. Critical roles of Aß oligomer deposited and ganglioside GM1 could be formed as "seed" from insoluble GAß polymer in initiating the pathogenic process, while tau might also mediate SPLs and their toxicity. The interaction between ceramide and α-Synuclein (α-Syn) accelerates the aggregation of ferroptosis and exacerbates the pathogenesis of AD. For instance, reducing the levels of SPLs can mitigate α-Syn accumulation and inhibit AD progression. Meanwhile, loss of SPLs may inhibit the expression of APOE4 and confer protection against AD, while the loss of APOE4 expression also disrupts SPLs homeostasis. Moreover, the heightened activation of sphingomyelinase promotes the ferroptosis signaling pathway, leading to exacerbated AD symptoms. Ferroptosis plays a vital role in the pathological progression of AD by influencing Aß, tau, APOE, and α-Syn. Conversely, the development of AD also exacerbates the manifestation of ferroptosis and SPLs. We are compiling the emerging techniques (Derivatization and IM-MS) of sphingolipidomics, to overcome the challenges of AD diagnosis and treatment. In this review, we examined the intricate neuro-mechanistic interactions between SPLs and Aß, tau, α-Syn, APOE, and ferroptosis, mediating the onset of AD. Furthermore, our findings highlight the potential of targeting SPLs as underexplored avenue for devising innovative therapeutic strategies against AD.

Learn Zero-Constraint-Violation Safe Policy in Model-Free Constrained Reinforcement Learning.

We focus on learning the zero-constraint-violation safe policy in model-free reinforcement learning (RL). Existing model-free RL studies mostly use the posterior penalty to penalize dangerous actions, which means they must experience the danger to learn from the danger. Therefore, they cannot learn a zero-violation safe policy even after convergence. To handle this problem, we leverage the safety-oriented energy functions to learn zero-constraint-violation safe policies and propose the safe set actor-critic (SSAC) algorithm. The energy function is designed to increase rapidly for potentially dangerous actions, locating the safe set on the action space. Therefore, we can identify the dangerous actions prior to taking them and achieve zero-constraint violation. Our major contributions are twofold. First, we use the data-driven methods to learn the energy function, which releases the requirement of known dynamics. Second, we formulate a constrained RL problem to solve the zero-violation policies. We prove that our Lagrangian-based constrained RL solutions converge to the constrained optimal zero-violation policies theoretically. The proposed algorithm is evaluated on the complex simulation environments and a hardware-in-loop (HIL) experiment with a real autonomous vehicle controller. Experimental results suggest that the converged policies in all environments achieve zero-constraint violation and comparable performance with model-based baseline.

Association between temperature and mortality: a multi-city time series study in Sichuan Basin, southwest China.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS: Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.

Disease-Associated Streptococcus pneumoniae Genetic Variation.

Streptococcus pneumoniae is an opportunistic pathogen that causes substantial illness and death among children worldwide. The genetic backgrounds of pneumococci that cause infection versus asymptomatic carriage vary substantially. To determine the evolutionary mechanisms of opportunistic pathogenicity, we conducted a genomic surveillance study in China. We collected 783 S. pneumoniae isolates from infected and asymptomatic children. By using a 2-stage genomewide association study process, we compared genomic differences between infection and carriage isolates to address genomic variation associated with pathogenicity. We identified 8 consensus k-mers associated with adherence, antimicrobial resistance, and immune modulation, which were unevenly distributed in the infection isolates. Classification accuracy of the best k-mer predictor for S. pneumoniae infection was good, giving a simple target for predicting pathogenic isolates. Our findings suggest that S. pneumoniae pathogenicity is complex and multifactorial, and we provide genetic evidence for precise targeted interventions.

Developing a novel SARS-CoV-2 risk index to predict the prognostic and therapeutic effects in acute myeloid leukemia.

There is growing evidence of a strong association between SARS-CoV-2 and cancer prognosis and treatment outcome. However, there are no reliable SARS-CoV-2 assessment models to accurately predict prognostic and therapeutic effects in acute myeloid leukemia (AML). Here, differentially expressed genes associated with SARS-CoV-2 were detected, and multiple Cox regression methods were used to construct a SARS-CoV-2 risk index (SC2RI). Then, RT-qPCR was used to validate the gene expression levels in the AML samples. Finally, we explored how the SC2RI affected prognosis, immune infiltration, immunotherapy, and drug sensitivity in AML. We found that CYB5R3 and CLIP4 had been confirmed as hub genes in AML and were used to generate the SC2RI. The datasets indicated that the SC2RI had a superior predictive impact on the prognosis of AML. In addition, high expression of immune checkpoints and numerous immunological infiltrations were substantially correlated with a high SC2RI. However, it responded poorly to immune checkpoint blockade, which may be related to T-cell dysfunction, lack of effective antigens, and deficiency of synaptic capacity. Moreover, a high SC2RI was less susceptible to mTOR-related pathway medications but more sensitive to cell cycle suppressors. Therefore, categorization based on SC2RI could enhance the prognostic prediction of AML and help identify novel therapeutic approaches.

Comparative analysis of mitogenomes among three species of grasshoppers (Orthoptera: Acridoidea: Gomphocerinae) and their phylogenetic implications.

Whole mitochondrial genomes have been widely used in phylogenetic analysis, population genetics and biogeography studies. This study sequenced and characterized three complete mitochondrial genomes (Dasyhippus peipingensis, Myrmeleotettix palpalis, Aeropedellus prominemarginis) and determined their phylogenetic position in Acrididae. The length of the mitochondrial genomes ranged from 15,621-15,629 bp and composed of 13 PCGs, 2 rRNA, 22 tRNA genes and an AT control region. The arrangement and structure of the mitochondrial genomes were similar to those of other invertebrates. Comparative genomics revealed that the three mitochondrial genomes were highly conserved in terms of gene size, structure, and codon usage, all PCGs were purified selections with an ATN start codon and a TAN stop codon. All tRNAs could be folded into the typical clover-leaf structure, except tRNA Ser (AGN) that lacked a dihydrouridine (DHU) arm. Phylogenetic analysis based on 13 PCGs of 34 Acrididae species and seven outgroup species revealed that differences in the shape of antennae within the family Acrididae should be given less weight as a taxonomic character for higher-level classification. Moreover, the divergence time estimates indicates that in Gomphocerinae, the species with clubbed antennae were formed within the nearest 18 Mya, and Pacris xizangensis is more ancient.

Contaminant characterization of odor in soil of typical pesticide-contaminated site with shallow groundwater.

Odor emission from the soil of pesticide-contaminated sites is a prominent environmental problem in China, but there are very few researches about the component and spatial distribution of odorous substances in the soil of contaminated sites. In this paper, to investigate the odor pollution condition of an organophosphorus pesticide production site in a city of South China, the odor pollutants in the soil and soil gas were analyzed and the key odor-contributing substances were identified. Besides, the correlation between the concentrations of odorous substances in soil and soil gas was analyzed, and the measured results were compared with the predicted results by the linear model and DED model. An off-line soil gas sampling device was designed to collect the gas emitted from soil because the groundwater level in the site was too shallow to build a soil gas well. The key odor substances were screened from the detection results of soil gas via odor activity value (OAV) analysis, which revealed that the key odorous substances included benzene, ethylbenzene, ammonia, toluene, m,p-xylene, methyl sulfide, dimethyl disulfide, and formaldehyde. Furthermore, the spatial distribution of the odor substances in the soil of the pesticide-contaminated site was closely related to the layout and geologic structure of the site. The odor pollutants in soil were mainly distributed near the phosmet production workshop and the drainage ditch network. As for the deep distribution, the odorous substances were mainly enriched in the silty clay or clay layer (5.6-11 m), followed by the sludge layer (1-3.6 m). Finally, the predicted model (linear model and DED model) analysis suggested that the linear model was more suitable for predicting the concentration of odorous substances in the soil gas with the detection data of soil in this pesticide-contaminated site.

[Screening of pathogenic molecular markers of Staphylococcus aureus in children based on whole genome sequencing technology]. / åŸºäºŽå ¨åŸºå› ç»„æµ‹åºæŠ€æœ¯ç­›é€‰å„¿ç«¥é‡‘é»„è‰²è‘¡è„çƒèŒçš„è‡´ç— ç›¸å ³åˆ†å­æ ‡å¿—ç‰©.

OBJECTIVES: To explore the molecular characteristics of Staphylococcus aureus (S. aureus) in children, and to compare the molecular characteristics of different types of strains (infection and colonization strains) so as to reveal pathogenic molecular markers of S. aureus. METHODS: A cross-sectional study design was used to conduct nasopharyngeal swab sampling from healthy children in the community and clinical samples from infected children in the hospital. Whole genome sequencing was used to detect antibiotic resistance genes and virulence genes. A random forest method to used to screen pathogenic markers. RESULTS: A total of 512 S. aureus strains were detected, including 272 infection strains and 240 colonization strains. For virulence genes, the carrying rates of enterotoxin genes (seb and sep), extracellular enzyme coding genes (splA, splB, splE and edinC), leukocytotoxin genes (lukD, lukE, lukF-PV and lukS-PV) and epidermal exfoliating genes (eta and etb) in infection strains were higher than those in colonization strains. But the carrying rates of enterotoxin genes (sec, sec3, seg, seh, sei, sel, sem, sen, seo and seu) were lower in infection strains than in colonization strains (P<0.05). For antibiotic resistance genes, the carrying rates of lnuA, lnuG, aadD, tetK and dfrG were significantly higher in infection strains than in colonization strains (P<0.05). The accuracy of cross-validation of the random forest model for screening pathogenic markers of S. aureus before and after screening was 69% and 68%, respectively, and the area under the curve was 0.75 and 0.70, respectively. The random forest model finally screened out 16 pathogenic markers (sem, etb, splE, sep, ser, mecA, lnuA, sea, blaZ, cat(pC233), blaTEm-1A, aph(3')-III, ermB, ermA, ant(9)-Ia and ant(6)-Ia). The top five variables in the variable importance ranking were sem (OR=0.40), etb (OR=3.95), splE (OR=1.68), sep (OR=3.97), and ser (OR=1.68). CONCLUSIONS: The random forest model can screen out pathogenic markers of S. aureus and exhibits a superior predictive performance, providing genetic evidence for tracing highly pathogenic S. aureus and conducting precise targeted interventions.

Osseointegration of functionally graded Ti6Al4V porous implants: Histology of the pore network.

The additive manufacturing of titanium into porous geometries offers a means to generate low-stiffness endosseous implants with a greater surface area available for osseointegration. In this work, selective laser melting was used to produce gyroid-based scaffolds with a uniform pore size of 300 µm or functionally graded pore size from 600 µm to 300 µm. Initial in vitro assessment with Saos-2 cells showed favourable cell proliferation at pore sizes of 300 and 600 µm. Following implantation into rabbit tibiae, early histological observations at four weeks indicated some residual inflammation alongside neovessel infiltration into the scaffold interior and some early apposition of mineralized bone tissue. At twelve weeks, both scaffolds were filled with a mixture of adipocyte-rich marrow, micro-capillaries, and mineralized bone tissue. X-ray microcomputed tomography showed a higher bone volume fraction (BV/TV) and percentage of bone-implant contact (BIC) in the implants with 300 µm pores than in the functionally graded specimens. In functionally graded specimens, localized BV/TV measurement was observed to be higher in the innermost region containing smaller pores (estimated at 300-400 µm) than in larger pores at the implant exterior. The unit cell topology of the porous implant was also observed to guide the direction of bone ingrowth by conducting along the implant struts. These results suggest that in vivo experimentation is necessary alongside parametric optimization of functionally graded porous implants to predict short-term and long-term bone apposition.

The association between perchlorate in drinking water and height and weight of children and adolescents in Southwest China: a retrospective cross-sectional study.

Objective: To investigate the association between the concentration of perchlorate in drinking water and the height and weight of children and adolescents in Sichuan Province. Methods: Perchlorate in the drinking water of 24 counties in Sichuan Province from 2021 to 2022 was detected and analyzed, 66 drinking water samples were collected, and the content of perchlorate in drinking water during the wet season and dry season was detected by ultra-high performance liquid chromatography in series. The linear mixed effect model was used to estimate the relationship between perchlorate in drinking water and the height and weight of 144,644 children and adolescents, and 33 pieces of local average wage data were used as confounding factors for quality control. Results: After controlling the age, gender, and local economic situation, we found that the concentration of perchlorate in drinking water increased by 10 µg/L is associated with a 1.0 cm decrease in height and a 1.6 kg decrease in weight in children and adolescents (p < 0.05). Conclusion: The concentration of perchlorate in drinking water may be negatively correlated with the height and weight of children.

Exploring the therapeutic potential of natural compounds modulating the endocannabinoid system in various diseases and disorders: review.

Cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes involved in the biosynthesis and degradation of the endocannabinoids make up the endocannabinoid system (ECS). The components of the ECS are proven to modulate a vast bulk of various physiological and pathological processes due to their abundance throughout the human body. Such discoveries have attracted the researchers' attention and emerged as a potential therapeutical target for the treatment of various diseases. In the present article, we reviewed the discoveries of natural compounds, herbs, herbs formula, and their therapeutic properties in various diseases and disorders by modulating the ECS. We also summarize the molecular mechanisms through which these compounds elicit their properties by interacting with the ECS based on the existing findings. Our study provides the insight into the use of natural compounds that modulate ECS in various diseases and disorders, which in turn may facilitate future studies exploiting natural lead compounds as novel frameworks for designing more effective and safer therapeutics.

Enhanced tumor immunotherapy by polyfunctional CD19-CAR T cells engineered to secrete anti-CD47 single-chain variable fragment.

A high recurrence rate of non-Hodgkin's lymphoma (NHL) following chimeric antigen receptor T (CAR T) cell treatment remains a bottleneck, and immunosuppressive tumor microenvironment (TME) compromising CAR T cell efficacy in NHL is the primary cause of relapse. Accordingly, modifying the structure of CAR T cells to attenuate the inhibitory effect of TME thus reducing recurrence rate is a valuable research topic. CD47 has been proved to be a promising therapeutic target and is crucial in regulating macrophage function. Herein, we engineered CD19-CAR T cells to secrete an anti-CD47 single-chain variable fragment (scFv) and validated their function in enhancing antitumor efficacy, regulating T cells differentiation, modifying phagocytosis and polarization of macrophages by in vitro and in vivo researches. The efficacy was analogous or preferable to the combination of CAR T cells and CD47 antibody. Of note, anti-CD47 scFv secreting CAR T cells exert a more potent immune response following specific antigen stimulation compared with parental CAR T cells, characterized by more efficient degranulation and cytokine production with polyfunctionality. Furthermore, locally delivering anti-CD47 by CAR T cells potentially limits toxicities relevant to systemic antibody treatment. Collectively, our research provides a more effective and safer CAR T cell transformation method for enhancing tumor immunotherapy.