Diversity within the species Clostridium butyricum: pan-genome, phylogeny, prophage, carbohydrate utilization, and antibiotic resistance.

AIMS: Clostridium butyricum has been recognized as a strong candidate for the "next generation of probiotics" due to its beneficial roles on humans. Owing to our current understanding of this species is limited, it is imperative to unveil the genetic variety and biological properties of C. butyricum on sufficient strains. METHODS AND RESULTS: We isolated 53 C. butyricum strains and collected 25 publicly available genomes to comprehensively assess the genomic and phenotypic diversity of this species. Average nucleotide identity and phylogeny suggested that multiple C. butyricum strains might share the same niche. Clostridium butyricum genomes were replete with prophage elements, but the CRISPR-positive strain efficiently inhibited prophage integration. Clostridium butyricum utilizes cellulose, alginate, and soluble starch universally, and shows general resistance to aminoglycoside antibiotics. CONCLUSIONS: Clostridium butyricum exhibited a broad genetic diversity from the extraordinarily open pan-genome, extremely convergent core genome, and ubiquitous prophages. In carbohydrate utilization and antibiotic resistance, partial genotypes have a certain guiding significance for phenotypes.

Quantifying human mixing patterns in Chinese provinces outside Hubei after the 2020 lockdown was lifted.

BACKGROUND: Contact patterns play a key role in the spread of respiratory infectious diseases in human populations. During the COVID-19 pandemic, the regular contact patterns of the population have been disrupted due to social distancing both imposed by the authorities and individual choices. Many studies have focused on age-mixing patterns before the COVID-19 pandemic, but they provide very little information about the mixing patterns in the COVID-19 era. In this study, we aim at quantifying human heterogeneous mixing patterns immediately after lockdowns implemented to contain COVID-19 spread in China were lifted. We also provide an illustrative example of how the collected mixing patterns can be used in a simulation study of SARS-CoV-2 transmission. METHODS AND RESULTS: In this work, a contact survey was conducted in Chinese provinces outside Hubei in March 2020, right after lockdowns were lifted. We then leveraged the estimated mixing patterns to calibrate a mathematical model of SARS-CoV-2 transmission. Study participants reported 2.3 contacts per day (IQR: 1.0-3.0) and the mean per-contact duration was 7.0 h (IQR: 1.0-10.0). No significant differences in average contact number and contact duration were observed between provinces, the number of recorded contacts did not show a clear trend by age, and most of the recorded contacts occurred with family members (about 78%). The simulation study highlights the importance of considering age-specific contact patterns to estimate the COVID-19 burden. CONCLUSIONS: Our findings suggest that, despite lockdowns were no longer in place at the time of the survey, people were still heavily limiting their contacts as compared to the pre-pandemic situation.

Genome-Wide Identification and Expression Analysis of LBD Transcription Factor Genes in Passion Fruit (Passiflora edulis).

The lateral organ boundary domain (LBD) gene is a plant-specific transcription factor that plays a crucial role in plant growth and development, including the development of lateral vegetative organs such as leaf and root development, as well as floral organs such as sepal, petal, and pollen development. Passion fruit is a tropical fruit with important agricultural, economic and ornamental value. However, there is no systematic research report available on the LBD gene family of passion fruit. In this study, a genome-wide analysis of passion fruit LBD genes identified 33 PeLBDs that were unevenly distributed across nine chromosomes. According to phylogenetic and gene structure analysis, PeLBDs were divided into two categories: Class I (27) and Class II (6). Homologous protein modeling results showed that the gene members of the two subfamilies were structurally and functionally similar. Cis-acting element and target gene prediction analysis suggested that PeLBDs might participate in various biological processes by regulating diverse target genes involved in growth and development, metabolism, hormones and stress response. Collinearity analysis indicated that the expansion of the PeLBD gene family likely took place mainly by segmental duplication, and some duplicated gene pairs such as PeLBD13/15 might show functional redundancy, while most duplicated gene pairs such as PeLBD8/12 showed different expression profiles indicating their functional diversification. After filtering low expressed genes, all Class Id PeLBDs were more highly expressed during pollen development. At the same, all Class Ic and many other PeLBDs were relatively highly expressed during ovule development, similar with their homologous LBD genes in Arabidopsis, indicating their potential regulatory roles in reproductive tissue development in passion fruit. PeLBDs that were highly expressed in floral tissues were also expressed at a higher level in tendrils with some differences, indicating the close relationships of tendrils to floral tissues. Some genes such as PeLBD23/25 might be simultaneously related to floral development and leaf early formation in passion fruit, while other PeLBDs showed a strong tissue-specific expression. For example, PeLBD17/27/29 were specifically expressed in floral tissues, while PeLBD11 were only highly expressed in fruit, suggesting their specific function in the development of certain tissues. A qRT-PCR was conducted to verify the expression levels of six PeLBDs in different tissues. Our analysis provides a basis for the functional analysis of LBD genes and new insights into their regulatory roles in floral and vegetative tissue development.

COFT-AD: COntrastive Fine-Tuning for Few-Shot Anomaly Detection.

Existing approaches towards anomaly detection (AD) often rely on a substantial amount of anomaly-free data to train representation and density models. However, large anomaly-free datasets may not always be available before the inference stage; in which case an anomaly detection model must be trained with only a handful of normal samples, a.k.a. few-shot anomaly detection (FSAD). In this paper, we propose a novel methodology to address the challenge of FSAD which incorporates two important techniques. Firstly, we employ a model pre-trained on a large source dataset to initialize model weights. Secondly, to ameliorate the covariate shift between source and target domains, we adopt contrastive training to fine-tune on the few-shot target domain data. To learn suitable representations for the downstream AD task, we additionally incorporate cross-instance positive pairs to encourage a tight cluster of the normal samples, and negative pairs for better separation between normal and synthesized negative samples. We evaluate few-shot anomaly detection on 3 controlled AD tasks and 4 real-world AD tasks to demonstrate the effectiveness of the proposed method.

DDT-Net: Dose-Agnostic Dual-Task Transfer Network for Simultaneous Low-Dose CT Denoising and Simulation.

Deep learning (DL) algorithms have achieved unprecedented success in low-dose CT (LDCT) imaging and are expected to be a new generation of CT reconstruction technology. However, most DL-based denoising models often lack the ability to generalize to unseen dose data. Moreover, most simulation tools for LDCT typically operate on proprietary projection data, which is generally not accessible without an established collaboration with CT manufacturers. To alleviate these issues, in this work, we propose a dose-agnostic dual-task transfer network, termed DDT-Net, for simultaneous LDCT denoising and simulation. Concretely, the dual-task learning module is constructed to integrate the LDCT denoising and simulation tasks into a unified optimization framework by learning the joint distribution of LDCT and NDCT data. We approximate the joint distribution of continuous dose level data by training DDT-Net with discrete dose data, which can be generalized to denoising and simulation of unseen dose data. In particular, the mixed-dose training strategy adopted by DDT-Net can promote the denoising performance of lower-dose data. The paired dataset simulated by DDT-Net can be used for data augmentation to further restore the tissue texture of LDCT images. Experimental results on synthetic data and clinical data show that the proposed DDT-Net outperforms competing methods in terms of denoising and generalization performance at unseen dose data, and it also provides a simulation tool that can quickly simulate realistic LDCT images at arbitrary dose levels.

The Effect of Work Stress on the Well-Being of Primary and Secondary School Teachers in China.

Primary and secondary school teachers face increasing work stress, and more attention needs to be paid to their well-being. The present study was conducted to analyze the influence of work stress on the well-being of such teachers in China, and to explore the effects of family-work conflict and a self-transcendent meaning of life. A total of 562 primary and secondary school teachers completed questionnaires assessing work stress, family-work conflict, and a self-transcendent meaning of life (including grasping the meaning of failure and detachment from success or failure) as potential predictors of well-being. Work stress negatively predicted teachers' well-being; family-work conflict mediated this relationship and a self-transcendent meaning of life moderated it. The results of this study can be used as a reference for education departments seeking to intervene to prevent teachers from developing well-being problems from the perspective of a self-transcendent meaning of life.

COVID-19 spreading patterns in family clusters reveal gender roles in China.

Understanding different gender roles forms part of the efforts to reduce gender inequality. This paper analyses COVID-19 family clusters outside Hubei Province in mainland China during the 2020 outbreak, revealing significant differences in spreading patterns across gender and family roles. Results show that men are more likely to be the imported cases of a family cluster, and women are more likely to be infected within the family. This finding provides new supportive evidence of the 'men as breadwinner and women as homemaker' (MBWH) gender roles in China. Further analyses reveal that the MBWH pattern is stronger in eastern than in western China, stronger for younger than for elder people. This paper offers not only valuable references for formulating gender-differentiated epidemic prevention policies but also an exemplification for studying group differences in similar scenarios.

Clostridium butyricum Reduces Obesity in a Butyrate-Independent Way.

Accumulating evidence from recent studies links the gut microbiota to obesity, and microbiome therapy has been examined as a treatment. Clostridium butyricum (C. butyricum), an intestinal symbiont, protects the host from a range of diseases. Studies have shown a negative correlation between the relative abundance of C. butyricum and a predisposition for obesity. However, the physiological function and material basis of C. butyricum for obesity are unclear. Here, five C. butyricum isolates were administered to mice on a high-fat diet (HFD) to determine their anti-obesity effects. All isolates suppressed the formation and inflammation of subcutaneous fat, and the two effective strains considerably reduced weight gain and ameliorated dyslipidemia, hepatic steatosis, and inflammation. These positive effects were not achieved by increasing the concentration of intestinal butyrate, and the effective strains could not be replaced by sodium butyrate (NaB). We also discovered that oral supplementation with the two most effective strains changed the metabolism of tryptophan and purine and altered the composition of the gut microbiota. In summary, C. butyricum improved the metabolic phenotypes under the HFD by controlling the composition of the gut microbiota and modulating intestinal metabolites, thereby demonstrating its ability to fight obesity and providing a theoretical foundation for microbial preparations production.

Clostridium butyricum Strain CCFM1299 Reduces Obesity via Increasing Energy Expenditure and Modulating Host Bile Acid Metabolism.

Clostridium butyricum is a butyrate-producing microorganism which has beneficial effects on various diseases, including obesity. In our previous study, the anti-obesity Clostridium butyricum strain CCFM1299 (C20_1_1) was selected, but its anti-obesity mechanism was not clarified. Herein, CCFM1299 was orally administrated to high-fat-diet-treated C57BL/6J mice for 12 weeks to uncover the way the strain alleviates obesity. The results indicated that CCFM1299 alleviated obesity through increasing the energy expenditure and increasing the expression of genes related to thermogenesis in brown adipose tissue (BAT). Moreover, strain CCFM1299 could also affect the expression of immune-related genes in epididymal white adipose tissue (eWAT). This immunomodulatory effect might be achieved through its influence on the complement system, as the expression of the complement factor D (CFD) gene decreased significantly. From the view of metabolites, CCFM1299 administration increased the levels of ursodeoxycholic acid (UDCA) in feces and taurohyodeoxycholic acid (THDCA) in serum. Together, the anti-obesity potential of CCFM1299 might be attributed to the increase in energy consumption, the regulation of immune-related gene expression in eWAT, and the alteration of bile acid metabolism in the host. These provided new insights into the potential application of anti-obesity microbial preparations and postbiotics.

Impaired histone inheritance promotes tumor progression.

Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact of aberrant parental histone partition on human disease such as cancer is largely unknown. In this study, we construct a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast cancer cells. The resulting impaired histone inheritance reprograms the histone modification landscapes of progeny cells, especially the repressive histone mark H3K27me3. Lower H3K27me3 levels derepress the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. These epigenetic changes confer fitness advantages to some newly emerged subclones and consequently promote tumor growth and metastasis after orthotopic implantation. In summary, our results indicate that impaired inheritance of parental histones can drive tumor progression.

Surface Properties of Alkyldi(oxyethylene) ß-D-Maltoside.

A series of nonionic disaccharide-based surfactants alkyldi(oxyethylene) ß-d-maltosides (4a-4h, n = 6-16) were synthesized, and their physicochemical properties were further investigated. Six ß-D-maltosides (4c-4h, n = 8-16) exhibited a fan-shaped texture feature, whereas hexyldi(oxyethylene) ß-D-maltoside (4a) had the strongest hygroscopicity. Owing to the incorporation of the hydrophilic dioxyethyl spacer (-(OCH2CH2)2-), the related water solubility improved significantly. Tetradecyldi(oxyethylene) ß-D-maltoside (4g) had good water solubility, whereas hexadecyldi(oxyethylene) ß-D-maltoside (4h) had weak water solubility. Meanwhile, the surface tension of ß-D-maltosides (4a-4g, n = 6-14) had a decreasing tendency with increasing the alkyl chain length, whereas 4g had the best surface activity. Furthermore, decyldi(oxyethylene) ß-D-maltoside (4e) had the best foaming ability and foam stability. Dodecyldi(oxyethylene) ß-D-maltoside (4f) had the best emulsifying property in the rapeseed oil/water system. In contrast, both ammonium dodecyl sulfate (NH4DS)/4f and cetyltrimethylammonium chloride (CTAC)/4f binary surfactant systems showed a synergistic effect in surface activity because the CCMC/CMCidmix was <1. NaCl impacted the surface activity of the aqueous 4f solution through salt-surfactant synergistic effects. The results showed that such surfactants should have potential applications in the related field in the future.

Association between Primary Care Utilization and Emergency Room or Hospital Inpatient Services Utilization among the Middle-Aged and Elderly in a Self-Referral System: Evidence from the China Health and Retirement Longitudinal Study 2011-2018.

With rapid economic growth and aging, hospital inpatient and emergency services utilization has grown rapidly, and has emphasized an urgent requirement to adjust and optimize the structure of health service utilization. Studies have shown that primary care is an effective way to reduce inpatient and emergency room (ER) service utilization. This study aims to examine whether middle-aged and elderly individuals who selected primary care outpatient services in the last month had less ER and hospital inpatient service utilization than those who selected hospitals outpatient services via the self-referral system. Data were obtained from four waves of the nationally representative China Health and Retirement Longitudinal Study (CHARLS). We pooled respondents who had outpatient visits and were aged 45 years and above. We used logistic regressions to explore the association between types of outpatient and ER visits or hospitalization, and then used zero-truncated negative binomial regression to examine the impact of outpatient visit types on the number of hospitalizations and the length of hospitalization days. A trend test was used to explore the trend of outpatient visit types and the ER or hospital inpatient services utilization with the increase in outpatient visits. Among the 7544 respondents in CHARLS, those with primary care outpatient visits were less likely to have ER visits (adjusted OR = 0.141, 95% CI: 0.101-0.194), hospitalization (adjusted OR = 0.623, 95% CI: 0.546-0.711), and had fewer hospitalization days (adjusted IRR = 0.886, 95% CI: 0.81-0.969). The trend test showed that an increase in the number of total outpatient visits was associated with a lower hospitalizations (p = 0.006), but a higher odds of ER visits (p = 0.023). Our findings suggest that policy makers need to adopt systematic policies that focus on restructuring and balancing the structure of resources and service utilization in the three-tier healthcare system.

Surface Properties and Liquid Crystal Properties of Alkyltetra(oxyethyl) ß-d-Glucopyranoside.

Hydrophilic alkyl polyglycosides (APGs) and alkyl glycosides (AGs) with anomeric pure are a class of important substitutes for petroleum-based surfactants. Improving their water solubility should make such hydrophilic glycosurfactants have more excellent potential application value. To solve the inherent problem of poor water solubility of traditional alkyl ß-d-glucopyranoside (5), a series of alkyltetra(oxyethyl) ß-d-glucopyranosides (4a-4g, n = 7-18) were successfully synthesized by introducing tetra(oxyethylene) fragments to carry out the structural modification. The relationship between the related structure and the physicochemical properties was further investigated, including their hydrophilic-lipophilic balance (HLB), water-solubility, foaming performance, emulsification, hygroscopicity, surface activity, and thermotropic/lyotropic liquid crystal phase behavior. The results showed that the water solubility gradually decreased as the alkyl chain length increased due to the gradual decrease of their HLB number. Octadecyltetra(oxyethyl) ß-d-glucopyranoside (4g, n = 18) was found to be insoluble in water at 25 °C. Taken together, long-chain alkyl glycosides had good foaming properties and excellent emulsifying properties. Among them, dodecyltetra(oxyethyl) ß-d-glucopyranoside (4d, n = 12) had the best foaming performance. In the rapeseed oil/water system, cetyltetra(oxyethyl) ß-d-glucopyranoside (4f, n = 16) had the best emulsifying ability. With the increase of the alkyl chain length, the critical micelle concentration (Ccmc), γcmc, Γmax, and hygroscopicity of this series of glycosides showed a downward trend. Differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) showed that the thermal stability increased with the increase of the alkyl chain length, and alkyltetra(oxyethyl) ß-d-glucopyranosides (4d-4g, n = 12-18) had the corresponding melting points and clearing points. Alkyltetra(oxyethyl) ß-d-glucopyranosides (4b-4g, n = 8-18) formed a smectic phase with a typical fan-shaped and focal conic texture during the cooling process. In the water contact experiments, it was found that glycosides (4b-4g, n = 8-18) at high concentrations transformed into various lyotropic liquid crystal including hexagonal phase, bicontinuous cubic phase, and lamellar phase phases. Therefore, such green nonionic glycosurfactants alkyltetra(oxyethyl) ß-d-glucopyranosides should have potential practical application prospects.

Effect of Family Practice Contract Services on the Perceived Quality of Primary Care among Patients with Multimorbidity: A Cross-Sectional Study in Guangdong, China.

Family practice contract services, an important primary-care reform policy for improving primary healthcare quality in China, incorporate patients with multiple chronic conditions into the priority coverage groups and focus on their management. This study aims to explore the family practice contract services' effectiveness in improving the quality of primary care experienced by this population. A cross-sectional study using a three-stage sampling was conducted from January to March 2019 in Guangdong, China. A multivariable linear regression, including interaction terms, was applied to examine the associations between the contract services and primary care quality among people with different chronic conditions. The process quality of primary care was measured in six dimensions using the validated assessment survey of primary care (ASPC) scale. People with contract services scored higher in terms of quality of primary care than those without contract services. Contract services moderated the association between chronic condition status and primary care quality. Significantly positive interactions were observed in the patient-centred care dimension and negative interactions were reflected in the accessibility dimension. Our findings suggest that family practice contract services play a crucial role in improving patient-perceived primary care quality and provide emerging evidence that patients with multimorbidity tend to benefit more from the services, especially in patient-centred care.

The complete chloroplast genome sequence of Alniphyllum fortunei (Styracaceae) from Fujian, China.

Alniphyllum fortunei is a subtropical tree species, a large deciduous tree with a tall and straight trunk, which is an excellent fast-growing and broad-leaved tree species with a wide range of uses we resequenced complete chloroplast (cp) genome of A. fortunei from Fujian, China. The whole genome was 154,166 bp in length, consisting of a pair of inverted repeats (IR 26,658 bp), a large single-copy region (LSC 82,438 bp), and a small single-copy region (SSC 18,367 bp). The complete genome contained 139 genes, including 89 protein-coding genes, 40 tRNA, and 8 rRNA genes. The phylogenetic analyses based on the complete chloroplast genome sequence provided solid evidence that A. fortunei has a close relationship with A. pterospermum and Bruinsmia polysperma.

Association between Primary Healthcare and Medical Expenditures in a Context of Hospital-Oriented Healthcare System in China: A National Panel Dataset, 2012-2016.

Total health expenditure in China has grown considerably since a new round of health system reform was enacted in 2009. Researchers have shown that strengthening primary healthcare may be an option for countries to solve the rapid expansion of their medical expenditures. This study was designed to explore the association between the strength of primary healthcare and medical expenditures, in the context of the hospital-oriented healthcare system in China. A longitudinal ecological study was conducted using a 5-year panel dataset of 27 provinces in mainland China. The linear mixed effects regression model was used to assess the effects of primary healthcare-related metrics on medical expenditures, controlling for the provincial level specialty care physician supply and socio-economic parameters. All of the three primary healthcare-related metrics showed negative associations with the two medical expenditure parameters. Primary care physicians per 10,000 population was significantly associated with the per capita hospital medical expenditures (p < 0.05), and the percentage of public health expenditure in total health expenditure was significantly associated with both per capita total medical expenditure and per capita hospital medical expenditures (p < 0.01 for both). Our study found negative associations between the primary healthcare capacity and medical expenditure in the context of hospital-oriented healthcare systems in China, adding to the previous evidence that primary healthcare may play a positive role in reducing medical expenditure. Policies on increasing the primary care physician supply and the public share of total health expenditure should be conducted to strengthen the primary healthcare system. With the gradual advance of medical reform and the policy inclination to primary healthcare, this will play a more important role in controlling the rapid growth of medical expenditure.

Preliminary prediction of the basic reproduction number of the Wuhan novel coronavirus 2019-nCoV.

OBJECTIVES: To estimate the basic reproduction number of the Wuhan novel coronavirus (2019-nCoV). METHODS: Based on the susceptible-exposed-infected-removed (SEIR) compartment model and the assumption that the infectious cases with symptoms occurred before 26 January, 2020 are resulted from free propagation without intervention, we estimate the basic reproduction number of 2019-nCoV according to the reported confirmed cases and suspected cases, as well as the theoretical estimated number of infected cases by other research teams, together with some epidemiological determinants learned from the severe acute respiratory syndrome (SARS). RESULTS: The basic reproduction number fall between 2.8 and 3.3 by using the real-time reports on the number of 2019-nCoV-infected cases from People's Daily in China and fall between 3.2 and 3.9 on the basis of the predicted number of infected cases from international colleagues. CONCLUSIONS: The early transmission ability of 2019-nCoV is close to or slightly higher than SARS. It is a controllable disease with moderate to high transmissibility. Timely and effective control measures are needed to prevent the further transmissions.