Combinatorial discovery of antibacterials via a feature-fusion based machine learning workflow.

The discovery of new antibacterials within the vast chemical space is crucial in combating drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). However, the traditional approach of screening the entire chemical library in an ergodic manner can be laborious and time-consuming. Machine learning-assisted screening of antibacterials alleviates the exploration effort but suffers from the lack of reliable and related datasets. To address these challenges, we devised a combinatorial library comprising over 110 000 candidates based on the Ugi reaction. A focused library was subsequently generated through uniform sampling of the entire library to narrow down the preliminary screening scale. A novel feature-fusion architecture called the latent space constraint neural network was developed which incorporated both fingerprint and physicochemical molecular descriptors to predict the antibacterial properties. This integration allowed the model to leverage the complementary information provided by these descriptors and improve the accuracy of predictions. Three lead compounds that demonstrated excellent efficacy against MRSA while alleviating drug resistance were identified. This workflow highlights the integration of machine learning with the combinatorial chemical library to expedite high-quality data collection and extensive data mining for antibacterial screening.

In silico analysis of intestinal microbial instability and symptomatic markers in mice during the acute phase of severe burns.

BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.

Risk prediction for severe COVID-19 progressing to critical illness and death in the ICU and efficacy analysis of using traditional Chinese medicine.

To reveal the key factors influencing the progression of severe COVID-19 to critical illness and death in the intensive care unit (ICU) and to accurately predict the risk, as well as to validate the efficacy of treatment using traditional Chinese medicine (TCM), thus providing valuable recommendations for the clinical management of patients. A total of 189 patients with COVID-19 in 25 ICUs in Chongqing, China, were enrolled, and 16 eventually died. Statistical models shown that factors influencing the progression of COVID-19 to critical illness include the severity of illness at diagnosis, the mode of respiratory support, and the use of TCM. Risk factors for death include a history of metabolic disease, the use of antiviral drugs and TCM, and invasive endotracheal intubation. The area under curve of the noncollinearity model predicted the risk of progression to critical illness and the risk of death reached 0.847 and 0.876, respectively. The use of TCM is an independent protective factor for the prevention of the progression of severe COVID-19, while uncorrectable hypoxemia and invasive respiratory support are independent risk factors, and antiviral drugs can help reduce mortality. The multifactorial prediction model can assess the risk of critical illness and death in ICU COVID-19 patients, and inform clinicians in choosing the treatment options and medications.

Elucidating the mechanisms underlying astrocyte-microglia crosstalk in hippocampal neuroinflammation induced by acute diquat exposure.

The transition from paraquat (PQ) to diquat (DQ), both organic dication herbicides, in China has led to significant increases in the number of acute DQ poisoning cases. Case studies have shown that acute DQ poisoning resulted in injury to the central nervous system (CNS), but the mechanism underlying the injury remains to be explored. The present study aimed to investigate how DQ influenced purinergic signaling between astrocytes and microglia and whether extracellular ATP (eATP) was involved in promoting neuroinflammation induced by acute DQ toxicity through the activation of the P2X4/NLRP3 signaling pathway. We constructed a rat model of acute DQ toxicity to observe the pathological changes in hippocampal tissues after DQ exposure and measure the expression levels of IL-1ß and TNF-α in the hippocampal tissue. We also established an in vitro co-culture model of C6 astrocytes and BV-2 microglia using transwell chambers, measured the amount of eATP secreted into C6 astrocytes after DQ treatment, and assessed the inflammatory response and changes in the P2X4/NLRP3 signaling pathway in BV-2 microglia. The results showed that the neurons in the hippocampal tissue of rats exhibited loose arrangement, nuclear consolidation, and necrosis after DQ exposure, and IL-1ß and TNF-α levels were signification higher in the hippocampal tissue after DQ exposure. DQ exposure to the co-cultured cells induced an increase in ATP secretion from C6 astrocytes as well as a significant increase of P2X4, NLRP3, IL-1ß, and IL-18 expression in BV-2 microglia. In contrast, pretreatment of C6 astrocytes with apyrase (an ATP hydrolase) resulted in a significant decrease of P2X4, NLRP3, IL-1ß, and IL-18 expression in BV-2 microglia. Furthermore, inhibition of P2X4 expression in BV-2 microglia by transfection with si-P2X4 effectively reversed the increase of NLRP3, IL-1ß, and IL-18 in BV-2 microglia induced by DQ when co-cultured with C6 astrocytes. These results indicate that astrocytes can activate the P2X4/NLRP3 signaling pathway in microglia through the DQ-induced extracellular release of ATP to promote neuroinflammation in rat hippocampal tissue.

Inflammatory linear verrucous epidermal nevus in groin and labia with claudication: Successfully treated with photodynamic therapy.

SIGNIFICANCE: Inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon type of epidermal nevus and is refractory to therapy. We report the effectiveness of photodynamic therapy (PDT) for treating ILVEN with claudication in a young girl. ADDITIONAL CONTRIBUTIONS: We thank the patient for granting permission to publish this information. APPROACH: Aminolaevulinic Acid Hydrochloride (ALA) photodynamic therapy (PDT) was applied six times in 1-month interval. RESULTS: Most lesions and pruritus have subsided markedly, with mild scarring and a marked reduction in claudication. CONCLUSIONS: ALA PDT might be an effective and promising treatment for ILVEN in the future.

Phase retrieval for dual-projection pattern based on orthogonal frequency encoding to suppress superposing effects.

When grating patterns are simultaneously projected by a dual-projection structured-light system, interference-like blur and brightness overexposure in the superposed area often cause miscalculation of the phase of the grating pattern. In this study, we proposed a novel method, to the best of our knowledge, that utilizes orthogonal grating encoding to retrieve the phases of superposed grating patterns. Specifically, we determined the frequency of the dual-projection pattern based on the condition that enabled the separation of superposed orthogonal signals in wireless communication. Additionally, the maximum intensity of the projected pattern was determined using the intensity-saturation relationship. By performing a discrete Fourier transform on a series of superposed grating patterns, we obtained the wrapped phase of the corresponding projected grating patterns in the space-time dimension. Finally, we reconstructed the measured object by fusing the point clouds obtained from the dual-projection structured-light system. The experimental results demonstrated that the encoded orthogonal grating patterns could eliminate interference-like blurring and brightness overexposure during superposition and obtain high-precision phase maps and 3D reconstruction results, which provides the possibility for the simultaneous reconstruction of multiprojection structured light.

Facile Synthesis of Self-Targeted Zn2+ -Gallic acid Nanoflowers for Specific Adhesion and Elimination of Gram-Positive Bacteria.

Transition metal ions are served as disinfectant thousand years ago. However, the in vivo antibacterial application of metal ions is strongly restricted due to its high affinity with proteins and lack of appropriate bacterial targeting method. Herein, for the first time, Zn2+ -gallic acid nanoflowers (ZGNFs) are synthesized by a facile one-pot method without additional stabilizing agents. ZGNFs are stable in aqueous solution while can be easily decomposed in acidic environments. Besides, ZGNFs can specifically adhere onto Gram-positive bacteria, which is mediated by the interaction of quinone from ZGNFs and amino groups from teichoic acid of Gram-positive bacteria. ZGNFs exhibit high bactericidal effect toward various Gram-positive bacteria in multiple environments, which can be ascribed to the in situ Zn2+ release on bacterial surface. Transcriptome studies reveal that ZGNFs can disorder basic metabolic processes of Methicillin-resistant Staphylococcus aureus (MRSA). Moreover, in a MRSA-induced keratitis model, ZGNFs exhibit long-term retention in the infected corneal site and prominent MRSA elimination efficacy due to the self-targeting ability. This research not only reports an innovative method to prepare metal-polyphenol nanoparticles, but also provides a novel nanoplatform for targeted delivery of Zn2+ in combating Gram-positive bacterial infections.

EccBase: A high-quality database for exploration and characterization of extrachromosomal circular DNAs in cancer.

Extrachromosomal circular DNAs (eccDNAs) are widely observed in eukaryotes. Previous studies have demonstrated that eccDNAs are essential to cancer progression, and found that they can not only express in normal cells to regulate RNA, but also function differently in different tissues. It is of major interest to conduct computational or experiments assay to elucidate the mechanisms of eccDNA function, uncover key eccDNAs associated with diseases, and even develop related algorithms for liquid biopsy. Naturally, a comprehensive eccDNAs data resource is urgently needed to provide annotation and analysis more in-depth research. In this study, we constructed the eccBase (http://www.eccbase.net) in literature curation and database retrieval, which was the first database mainly collecting eccDNAs from Homo sapiens (n = 754,391) and Mus musculus (n = 481,381). Homo sapiens eccDNAs were taken from 50 kinds of cancer tissue and/or cell line, and 5 kinds of healthy tissues. The Mus musculus eccDNAs were sourced from 13 kinds of healthy tissue and/or cell line. We thoroughly annotated all eccDNA molecules in terms of basic information, genomic composition, regulatory elements, epigenetic modifications, and raw data. EccBase provided users with the ability to browse, search, download for targets of interest, as well as similarity alignment by the integrated BLAST. Further, comparative analysis suggested the cancer eccDNA is composed of nucleosomes and is prominently derived from the gene-dense regions. We also initially revealed that eccDNAs are strongly tissue-specific. In short, we have started a robust database for eccDNA resource utilization, which may facilitate studying the role of eccDNA in cancer development and therapy, cell function maintenance, and tissue differentiation.

Trends and characteristics of multiple births in Baoan Shenzhen: A retrospective study over a decade.

Background: Shenzhen has the largest and youngest foreign population among all cities in China. The reproductive health of pregnant women from different backgrounds is a social issue that deserves attention. In the past decade, China has liberalized its population policies to stimulate population growth, and the proportion of multiple births has continued to increase. Method: This retrospective cohort included 526,654 newborns born in Baoan, Shenzhen, from January 1, 2009, to December 31, 2019, including 515,016 singletons and 11,638 twins or triplets. Univariate regression models were used to analyze the effects of maternal sociodemographic characteristics, physiological characteristics, medical history, antenatal care and other factors associated with single vs. multiple births and to elucidate the changing trends of different factors affecting multiple births in the past 11 years. Additionally, fetal development in multiple births was analyzed by generalized linear mixed models. Results: The rates of pregnancy complications, preterm birth, and advanced-age pregnancy were significantly higher in the multiple birth mothers than in single birth mothers, and more multiple pregnancies were achieved through assisted reproductive technologies. The rates of adverse outcomes such as stillbirth, malformation, hypoxia, and ultralow body weight in multiple fetuses were significantly higher than that in singleton fetuses. The trend analysis from 2009 to 2019 showed that the socioeconomic status and health level of mothers with multiple births improved over time, and the risk during pregnancy generally decreased. Simultaneously, the development indicators of multiple fetuses have improved year by year, and the proportion of adverse outcomes has also decreased significantly. A low pre-natal care utilization rate was shown to be detrimental to the development of multiple fetuses. Independent risk factors for hypoxia and very low birth weight were also identified. The differences in secular trends between two birth groups were further revealed by time series models. Conclusion: This study presented a comprehensive survey of multiple pregnancies in the area with the largest population inflow in China. This study identified the factors that affect the health of multiple birth mothers and their fetuses, particularly suggesting that preterm birth rates and the use of assisted reproduction remain high. The findings provide a basis for the formulation of individualized pre-natal care, assisted reproductive guidance and healthcare policies for multiple births.

Ozone causes depressive-like response through PI3K/Akt/GSK3ß pathway modulating synaptic plasticity in young rats.

Ozone pollution has been associated with several adverse effects, including memory impairment, intellectual retardation, emotional disturbances. However, the potential mechanisms remain uncertain. The present study aimed to investigate whether ozone (O3) regulates synaptic plasticity through PI3K/Akt/GSK3ß signaling pathway and induces neurobehavioral modifications among the young rats. In vivo, the newborn rats were used to construct the animal model of early postnatal O3 treatment. In vitro, this study measured the effect of different concentrations of serum from O3 treated rats on the viability of the PC12 cells, and investigated the modifications of synaptic plasticity and PI3K/Akt/GSK3ß signaling pathway in the hippocampus and PC12 cells after O3 treated. The results revealed significant depression-like behavior and increased hippocampal histopathological damage in the young rats after O3 treated. Compared with the control group, the expression levels of synaptic related proteins including Drebrin, PSD95, Synaptophysin and PIK3R1, p-Akt, and p-GSK3ß were decreased in the O3 treated group. In vitro assays, a significant reduction in Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß was found in PC12 cells after O3 serum treated. While 740Y-P (a specific PI3K activator) administered, the expression levels of Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß in the 740Y-P + O3 group were significantly elevated in vivo and vitro compared with the O3-only group. In addition, miRNAs modulating PIK3R1 were screened on bioinformatics website, the study found aberrant expression of miR-221-3p in the hippocampus and serum of O3 treated group. Inhibition of miR-221-3p expression effectively reversed the reduction of Drebrin, PSD95, Synaptophysin, PIK3R1, p-Akt, and p-GSK3ß in PC12 cells induced by O3 treatment. Altogether, these studies indicate that O3 restrained the expression of PI3K/Akt/GSK3ß signaling pathway and impaired synaptic plasticity that resulted in depressive-like behavior in young rats. Moreover, miR-221-3p plays an important role in this procedure by regulating PIK3R1.

SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface.

Genetic polymorphisms are associated with the development of nonalcoholic fatty liver disease (NAFLD). Semaphorin7a (Sema7a) deficiency in mouse peritoneal macrophages reduces fatty acid (FA) oxidation. Here, we identified 17 individuals with SEMA7A heterozygous mutations in 470 patients with biopsy-proven NAFLD. SEMA7A heterozygous mutations increased susceptibility to NAFLD, steatosis severity, and NAFLD activity scores in humans and mice. The Sema7aR145W mutation (equivalent to human SEMA7AR148W) significantly induced small lipid droplet accumulation in mouse livers compared with WT mouse livers. Mechanistically, the Sema7aR145W mutation increased N-glycosylated Sema7a and its receptor integrin ß1 proteins in the cell membranes of hepatocytes. Furthermore, Sema7aR145W mutation enhanced its protein interaction with integrin ß1 and PKC-α and increased PKC-α phosphorylation, which were both abrogated by integrin ß1 silencing. Induction of PKCα_WT, but not PKCα_dominant negative, overexpression induced transcriptional factors Srebp1, Chrebp, and Lxr expression and their downstream Acc1, Fasn, and Cd36 expression in primary mouse hepatocytes. Collectively, our findings demonstrate that the SEMA7AR148W mutation is a potentially new strong genetic determinant of NAFLD and promotes intrahepatic lipid accumulation and NAFLD in mice by enhancing PKC-α-stimulated FA and triglyceride synthesis and FA uptake. The inhibition of hepatic PKC-α signaling may lead to novel NAFLD therapies.

Porous Photo-Fenton Catalysts Rapidly Triggered by Levodopa-Based Mussel-Inspired Coatings for Enhanced Dye Degradation and Sterilization.

The advanced oxidation process of the photo-Fenton reaction can produce hydroxyl radicals with extremely strong oxidizing properties for the efficient and green degradation of various chemical and microbial pollutants. Herein, we report an approach to fabricating heterogeneous Fenton catalysts of ß-FeOOH nanorods on porous substrates triggered by mussel-inspired coatings of levodopa (3,4-dihydroxy-phenyl-l-alanine, l-DOPA) and polyethylenimine (PEI) for efficient photocatalytic dyes' degradation and sterilization. The l-DOPA-based coatings not only promote the formation and immobilization of ß-FeOOH nanorods on the porous substrates by strong coordination between catechol/carboxyl groups and Fe3+ but also improve the energy band structure of the Fenton catalysts through a valence band blue shift and band gap narrowing. The photo-Fenton catalysts prepared by the l-DOPA-based coatings exhibit high electron transport efficiency and improved utilization of sunlight. Only 2 h of mineralization is needed to fabricate these catalysts with excellent photocatalytic efficiency, in which the degradation efficiency of methylene blue can reach 99% within 30 min, whereas the sterilization efficiency of E. coli/S. aureus can reach 93%/94% within 20 min of the photo-Fenton reaction. Additionally, the prepared catalysts reveal a high photodegradation performance for various dyes including methylene blue, methyl blue, methyl orange, direct yellow, and rhodamine B. Furthermore, the catalysts retain high dye degradation efficiencies of above 90% after five photodegradation cycles, indicating cycling performance and good stability.

Robust gamma correction based on chord distribution coding considering projector defocusing.

In phase-measurement profilometry (PMP), the gamma effect can cause severe nonlinear distortion of the phase pattern (i.e., water ripples on the surface profile). Gamma correction is an effective method to eliminate the gamma effects of commercial projectors. However, projector defocusing on the suppression of higher harmonics inevitably results in an estimated gamma deviation from the true value. In this study, gamma mapping is constructed using the duty ratio (DR) to code the chord distribution of the simulated distorted phase while considering projector defocusing. With the known gamma mapping, the accurate gamma is calculated by DR coding of the actual distorted phase under projector defocusing. Simulated experiments verified that the relative errors of the gamma calculated by the proposed method under different degrees of defocus were less than 3.5%. Furthermore, the experimental results demonstrate that the proposed gamma calculation method is robust to the defocus effect of the projector and that a smoother surface can be reconstructed after gamma correction.

JAK2/STAT3 pathway regulates microglia polarization involved in hippocampal inflammatory damage due to acute paraquat exposure.

OBJECTIVE: To explore the effects of acute paraquat (PQ) exposure on the phenotypic polarization of hippocampal microglia and its mechanism. METHODS: An acute PQ exposure rat model was established. Male SD rats were exposed to 0, 5, 25, and 50 mg/kg PQ, and brain hippocampal tissue was collected after 1, 3, and 7 days of exposure, respectively. Hippocampal pathological changes were examined by H&E staining, and immunohistochemistry (IHC) was used to detect changes in the number of Iba-1-positive cells, the average number of endpoints, and the average process length. The protein expression of Iba-1 was detected by western blotting. BV-2 microglia were treated with 0, 0.01, 0.025, 0.05, or 0.1 µmol/L PQ for 24 h. ELISA and western blotting assays were performed to detect the expression of TNF-α and IL-1ß in vivo and in vitro. The M1 microglia marker iNOS, the M2 microglia marker Arg-1, and the p-JAK2 and p-STAT3 protein were detected by western blotting. JAK2/STAT3 pathway activation role in regulating microglia phenotypic polarization was further validated in vivo and in vitro by JAK2-specific inhibitor AG490 administration. RESULTS: After acute PQ exposure, hippocampal neurons showed pathological changes such as loose arrangement and nuclear pyknosis, the number of Iba-1 positive cells and the expression of Iba-1 protein increased, and the average number of endpoints and average process length of microglia decreased. Histological examination revealed that compared with the control group, in the 50 mg/kg PQ group on the 3rd and 7th day, the expression of TNF-α, IL-1ß, and iNOS significantly increased, while that of Arg-1 significantly decreased. p-JAK2 and p-STAT3 expression significantly increased in the 50 mg/kg PQ group on the 1st, 3rd, and 7th day. In vitro, compared with the control group, the expression of TNF-α, IL-1ß, iNOS, p-JAK2, and p-STAT3 significantly increased, while Arg-1 expression was significantly reduced in the 0.025, 0.05, and 0.1 µmol/L PQ groups. After AG490 administration, the expression levels of p-JAK2, p-STAT3, iNOS, TNF-α, and IL-1ß in the AG490 +PQ group were significantly inhibited in vivo and in vitro compared with the PQ-only group. On the contrary, Arg-1 expression was significantly increased. CONCLUSION: Our results suggest that acute PQ exposure may induce M1-type polarization of hippocampal microglia by activating the JAK2/STAT3 pathway, which in turn releases pro-inflammatory factors such as TNF-α and IL-1ß, leading to hippocampal inflammatory damage.

Stillbirth trends by maternal sociodemographic characteristics among a large internal migrant population in Shenzhen, China, over a 10-year period: a retrospective study.

BACKGROUND: Cities such as Shenzhen in southern China have large immigrant populations, and the reproductive health issues of pregnant women in these populations have not received sufficient attention. Stillbirth seriously threatens their health and is becoming a social issue worthy of attention. We conducted this study to estimate the trend in stillbirths at 28 or more gestational weeks and the related sociodemographic characteristics of pregnant women among a large internal migrant population in South China. METHODS: A stillbirth is defined as a baby born with no signs of life after a given threshold, and are restricted to births of 28 weeks of gestation or longer, with a birth weight of at least 1000 g for international comparison. A population-based retrospective cohort of all births from January 2010 to December 2019 in Baoan, Shenzhen, was conducted using the Shenzhen Birth Registry Database. The overall stillbirth rate and year-specific stillbirth rate were calculated as the number of foetal deaths ≥28 gestational weeks or a birth weight ≥ 1000 g divided by the number of births over the last decade or in each year, respectively. The associations between the risk of stillbirth and maternal sociodemographic status were assessed using logistic regression. Spearman's rank correlation was calculated to evaluate the correlation between the economic status of the maternal birthplace and the stillbirth. RESULTS: An overall stillbirth rate of 4.5 per 1000 births was estimated in a total of 492,184 births in our final analysis. Migrant women accounted for 87% of the total population but had a higher stillbirth rate (4.8 per 1000 births) than the permanent population (2.8 per 1000 births). The stillbirth rate varied by region of maternal birthplace, from 4.1 per 1000 births in women from East China to 5.7 per 1000 births in women from West China. The GDP per capita of the maternal birthplace was strongly correlated with the stillbirth rate. CONCLUSIONS: Large disparities in the stillbirth rate exist between migrant and permanent populations and among regions of maternal birthplace in China. Strategies targeting migrant women based on their maternal birthplace are needed to further reduce the burden of stillbirth.

Stimuli-responsive nanoplatforms for antibacterial applications.

The continuously increasing bacterial resistance has become a big threat to public health worldwide, which makes it urgent to develop innovative antibacterial strategies. Nanotechnology-based drug delivery systems are considered as promising strategies in combating bacterial infections which are expected to improve the therapeutic efficacy and minimize the side effects. Unfortunately, the conventional nanodrug delivery systems always suffer from practical dilemmas, including incomplete and slow drug release, insufficient accumulation in infected sites, and weak biofilm penetration ability. Stimuli-responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles. In this review, we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area, including planktonic bacteria, intracellular bacteria, and bacterial biofilms. Taking advantage of the specific infected microenvironment (pH, enzyme, redox, and toxin), the mechanisms and strategies of the design of endogenous stimuli-responsive nanoplatforms are discussed, with an emphasis on how to improve the therapeutic efficacy and minimize side effects. How to realize controlled drug delivery using exogenous stimuli-responsive nanoplatforms especially light-responsive nanoparticles for improved antibacterial effects is another topic of this review. We especially highlight photothermal-triggered drug delivery systems by the combination of photothermal agents and thermo-responsive materials. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Pivotal Dominant Bacteria Ratio and Metabolites Related to Healthy Body Index Revealed by Intestinal Microbiome and Metabolomics.

Various body indexes, especially body fat percentage (BFP), are widely used as effective indicators to measure our health. BFP is used in medicine to assess obesity, which is a body fat mass disorder accompanied with changes of the gut microbiota. However, the relationship between BFP and the gut microbiota has not been studied so far. To address this problem, we examined how gut microbiota and metabolome associated with body indices in healthy people. Microbial and metabolomics data based on 16S rDNA sequencing and LC-MS were obtained from stool samples of 20 healthy adults. Bioinformatics analysis was performed to explore the correlations between the body indices and gut microbial characteristics. Significantly different microbes were further validated via qPCR. Differential characteristics were filtered by building machine learning models to predict body status. Our data showed that abundance of Prevotella and the Prevotella/Bacteroides (P/B) ratio in the gut were markedly higher in high-BFP individuals than in low-BFP individuals. Microbial and metabolomics data consistently suggested significant differences in fatty acid metabolism in stool samples from the two groups. The P/B ratio and fatty acids are discriminative for people with different index levels by cross validation tests with machine learning models. These results suggest using Prevotella and fecal fatty acids as predictors may offer an alternative method for evaluating health status or weight loss. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00989-5.

Predicting pneumonia during hospitalization in flail chest patients using machine learning approaches.

Objective: Pneumonia is a common pulmonary complication of flail chest, causing high morbidity and mortality rates in affected patients. The existing methods for identifying pneumonia have low accuracy, and their use may delay antimicrobial therapy. However, machine learning can be combined with electronic medical record systems to identify information and assist in quick clinical decision-making. Our study aimed to develop a novel machine-learning model to predict pneumonia risk in flail chest patients. Methods: From January 2011 to December 2021, the electronic medical records of 169 adult patients with flail chest at a tertiary teaching hospital in an urban level I Trauma Centre in Chongqing were retrospectively analysed. Then, the patients were randomly divided into training and test sets at a ratio of 7:3. Using the Fisher score, the best subset of variables was chosen. The performance of the seven models was evaluated by computing the area under the receiver operating characteristic curve (AUC). The output of the XGBoost model was shown using the Shapley Additive exPlanation (SHAP) method. Results: Of 802 multiple rib fracture patients, 169 flail chest patients were eventually included, and 86 (50.80%) were diagnosed with pneumonia. The XGBoost model performed the best among all seven machine-learning models. The AUC of the XGBoost model was 0.895 (sensitivity: 84.3%; specificity: 80.0%).Pneumonia in flail chest patients was associated with several features: systolic blood pressure, pH value, blood transfusion, and ISS. Conclusion: Our study demonstrated that the XGBoost model with 32 variables had high reliability in assessing risk indicators of pneumonia in flail chest patients. The SHAP method can identify vital pneumonia risk factors, making the XGBoost model's output clinically meaningful.

Fabrication of "Spongy Skin" on Diversified Materials Based on Surface Swelling Non-Solvent-Induced Phase Separation.

Porous surfaces have attracted tremendous interest for customized incorporation of functional agents on biomedical devices. However, the versatile preparation of porous structures on complicated devices remains challenging. Herein, we proposed a simple and robust method to fabricate "spongy skin" on diversified polymeric substrates based on non-solvent-induced phase separation (NIPS). Through the swelling and the subsequent phase separation process, interconnected porous structures were directly formed onto the polymeric substrates. The thickness and pore size could be regulated in the ranges of 5-200 and 0.3-0.75 µm, respectively. The fast capillary action of the porous structure enabled controllable loading and sustained release of ofloxacin and bovine albumin at a high loading dosage of 79.9 and 24.1 µg/cm2, respectively. We verified that this method was applicable to diversified materials including polymethyl methacrylate, polystyrene, thermoplastic polyurethane, polylactide acid, and poly(lactic-co-glycolic acid) and can be realized onto TCPS cell culture plates. This NIPS-based method is promising to generate porous surfaces on medical devices for incorporating therapeutic agents.

A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis.

Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis. WGS reveals a SEMA7AR148W homozygous mutation in a female child with elevated levels of serum ALT, AST, and total bile acid (TBA) of unknown etiology. This patient also carried a SLC10A1S267F allele, but Slc10a1S267F homozygous mice exhibited normal liver function. Similar to the child, Sema7aR145W homozygous mice displayed elevated levels of serum ALT, AST, and TBA. Remarkably, liver histology and LC-MS/MS analyses exhibited hepatocyte hydropic degeneration and increased liver bile acid (BA) levels in Sema7aR145W homozygous mice. Further mechanistic studies demonstrated that Sema7aR145W mutation reduced the expression of canalicular membrane BA transporters, bile salt export pump (Bsep), and multidrug resistance-associated protein-2 (Mrp2), causing intrahepatic cholestasis in mice. Administration with ursodeoxycholic acid and a dietary supplement glutathione improved liver function in the child. Therefore, Sema7aR145W homozygous mutation causes intrahepatic cholestasis by reducing hepatic Bsep and Mrp2 expression.