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Drug-induced liver injury (DILI) is one of the most common causes of a drug being withdrawn, and identifying the culprit drugs and the host factors at risk of causing DILI has become a current challenge. Recent studies have found that immune status plays a considerable role in the development of DILI. In this study, DILI-related differentially expressed genes mediated by immunoinflammatory cytokines were obtained from the Gene Expression Omnibus (GEO) database to predict the occurrence of DILI (named the DILI predictive gene set, DILI_PGS), and the predictability of the DILI_PGS was verified using the Connectivity Map (CMap) and LiverTox platforms. The results obtained DILI_PGS from the GEO database could predict 81.25% of liver injury drugs. In addition, the Coexpedia platform was used to predict the DILI_PGS-related characteristics of common host diseases and found that the DILI_PGS mainly involved immune-related diseases and tumor-related diseases. Then, animal models of immune stress (IS) and immunosuppressive (IP) were selected to simulate the immune status of the above diseases. Meanwhile, psoralen, a main component derived from Psoralea corylifolia Linn. with definite hepatotoxicity, was selected as an experimental drug with highly similar molecular fingerprints to three idiosyncratic hepatotoxic drugs (nefazodone, trovafloxacin, and nimesulide) from the same DILI_PGS dataset. The animal experiment results found a single administration of psoralen could significantly induce liver injury in IS mice, while there was no obvious liver function change in IP mice by repeatedly administering the same dose of psoralen, and the potential mechanism of psoralen-induced liver injury in IS mice may be related to regulating the expression of the TNF-related pathway. In conclusion, this study constructed the DILI_PGS with high accuracy to predict the occurrence of DILI and preliminarily identified the characteristics of host factors inducing DILI.

Phytoplasmas are phloem-limited plant pathogens, such as sugarcane white leaf (SCWL) phytoplasma, which are responsible for heavy economic losses to the sugarcane industry. Characterization of phytoplasmas has been limited because they cannot be cultured in vitro. However, with the advent of genome sequencing, different aspects of phytoplasmas are being investigated. In this study, we developed a DNA enrichment method for sugarcane white leaf (SCWL) phytoplasma, evaluated the effect of DNA enrichment via Illumina sequencing technologies, and utilized Illumina and Nanopore sequencing technologies to obtain the complete genome sequence of the “Candidatus Phytoplasma sacchari” isolate SCWL1 that is associated with sugarcane white leaf in China. Illumina sequencing analysis elucidated that only 1.21% of the sequencing reads from total leaf DNA were mapped to the SCWL1 genome, whereas 40.97% of the sequencing reads from the enriched DNA were mapped to the SCWL1 genome. The genome of isolate SCWL1 consists of a 538,951 bp and 2976 bp long circular chromosome and plasmid, respectively. We identified 459 protein-encoding genes, 2 complete 5S-23S-16S rRNA gene operons, 27 tRNA genes, and an incomplete potential mobile unit (PMU) in the circular chromosome. Phylogenetic analyses and average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values based on the sequenced genome revealed that SCWL phytoplasma and sugarcane grassy shoot (SCGS) phytoplasma belonged to the same phytoplasma species. This study provides a genomic DNA enrichment method for phytoplasma sequencing. Moreover, we report the first complete genome of a “Ca. Phytoplasma sacchari” isolate, thus contributing to future studies on the evolutionary relationships and pathogenic mechanisms of “Ca. Phytoplasma sacchari” isolates.

Hyperbaric oxygen therapy is a relatively safe treatment method that has been used for a long time in the clinic. It has been proven that it can enhance the sensitivity of radiotherapy and photodynamic therapy for cancer. However, there are few studies on hyperbaric oxygen and immunotherapy. In this article, we summarize that hyperbaric oxygen therapy regulates the tumor microenvironment through various pathways such as improving tumor hypoxia, targeting hypoxia-inducing factors, and generating reactive oxygen species. The change in the tumor microenvironment ultimately affects the curative effect of immunotherapy. Therefore, hyperbaric oxygen can influence immunotherapy by regulating the tumor microenvironment, providing a direction for the future development of immunotherapy.

BackgroundIncreasing evidence suggests that gut dysbiosis can directly or indirectly affect the immune system through the brain-gut axis and play a role in the occurrence and development of Multiple sclerosis (MS). Oxymatrine (OMAT) has been shown to ameliorate the symptoms of MS in the classical experimental autoimmune encephalomyelitis (EAE) model of MS, but whether its therapeutic role is through the correction of gut dysbiosis, is unclear.MethodsThe effects of OMAT on intestinal flora and short-chain fatty acids in EAE model mice were evaluated by 16S rRNA sequencing and GC-MS/MS, respectively, and the function change of the blood-brain barrier and intestinal epithelial barrier was further tested by immunohistochemical staining, Evans Blue leakage detection, and RT-qPCR.ResultsThe alpha and beta diversity in the feces of EAE mice were significantly different from that of the control group but recovered substantially after OMAT treatment. Besides, the OMAT treatment significantly affected the gut functional profiling and the abundance of genes associated with energy metabolism, amino acid metabolism, the immune system, infectious diseases, and the nervous system. OMAT also decreased the levels of isobutyric acid and isovaleric acid in EAE mice, which are significantly related to the abundance of certain gut microbes and were consistent with the reduced expression of TNF-a, IL-6, and IL-1b. Furthermore, OMAT treatment significantly increased the expression of ZO-1 and occludin in the brains and colons of EAE mice and decreased blood-brain barrier permeability.ConclusionOMAT may alleviate the clinical and pathological symptoms of MS by correcting dysbiosis, restoring gut ecological and functional microenvironment, and inhibiting immune cell-mediated inflammation to remodel the brain-gut axis.

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BackgroundAge-associated cognitive decline has become a major threat to both personal welfare and public health and can further develop into Dementia/Alzheimer’s disease. Sleep is significantly correlated with cognitive function, but both cognitive impairment and sleep problems increase with normal aging. This study explored how sleep duration affects cognitive performance among older adults in China.MethodsUsing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2014 and 2018, cognitive function was assessed via the Mini-Mental State Examination (MMSE), which included five domains: orientation, registration, attention or calculation, recall, and language. Logistic regression was used to examine whether the change in sleep duration was a risk factor for cognitive impairment. We also used multinomial logistic regression to study the impact of sleep duration and the changes in sleep duration on cognitive changes during the follow-up period.ResultsThe empirical study showed a U-shaped relationship between sleep duration and increased risk of cognitive impairment. Short (< 6 hours) and long (> 8 hours) sleep durations were positively associated with cognitive impairment. Tests of interactions between sleep duration and sleep quality showed that short sleep durations with fair sleep quality had an increased risk of cognitive impairment. Further, the participants were divided into three groups: normal cognition (MMSE > 24), mild cognitive impairment (MCI, 18 ≤ MMSE score ≤ 24), and severe cognitive impairment (MMSE < 18). First, of the participants with normal cognition at baseline, those who sleeping > 7 h at follow-up and > 7 h at both baseline and 4-year follow-up assessments could increase the risk of cognitive impairment. Second, for individuals with MCI at baseline, those who transitioned to sleeping > 7 h at follow-up period and > 7 h at both baseline and 4-year follow-up assessments had a lower chance of reverting to normal cognition.ConclusionExcessive sleep may be a major risk for cognitive impairment among older adults. Furthermore, a moderate amount of sleep could be a possible strategy to prevent cognitive impairment.

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Pulsed signal trains comprising clicks, buzzes, and burst-pulses play important roles in the life activities of odontocetes, but they have not been distinguished in Indo-Pacific humpback dolphins. Underwater vocalizations of this species were recorded from 27 September to 2 October 2019 in the Beibu Gulf, South China Sea. Pulsed signal trains were detected with variations in the pulsed signal number (range of 6–76), mean inter-pulse interval (IPIs_m: 0.1–315 ms), and mean duration (D ranged from tens to thousands of milliseconds). Principal component analysis and hierarchical cluster analysis based on six acoustic parameters in the pulsed signal trains identified three categories of trains designated as clicks, burst-pulses, and buzzes. Buzzes and burst-pulses (different from those described in previous research) were detected for the first time in Indo-Pacific humpback dolphins in China. The results indicated that the IPIs_m was longest for clicks but shortest for buzzes, and the D values were longer for both clicks and burst-pulses than buzzes. The three train types could be identified based on the IPIs_m, with threshold values of 4.9 and 15.5 ms. The significant variations in the three vocalization types were related to surface behaviors, and buzzes could have a special function in foraging by this species, thereby requiring further research. These findings may facilitate future quantitative evaluations of the echolocation performance in wild Indo-Pacific humpback dolphins and provide important guidance regarding acoustic observations and the identification of this species.

Phytoplasmas are important prokaryotic pathogenic bacteria without cell walls, which were formerly known as mycoplasma-like organisms, and belong to the Mollicutes class, Candidatus Phytoplasma genus. They are widely distributed in plants and insects, and can cause serious diseases in important food crops, vegetables, fruit trees, ornamental plants and trees, resulting in huge economic losses. To date, more than 100 phytoplasma diseases have been reported in China, which are distributed throughout the country. Jujube witches'-broom, paulownia witches'-broom, wheat blue dwarf, banana bunchy top, sugarcane white leaf, rice orange leaf and mulberry dwarf represent the phytoplasma diseases causing the most serious damage in China. New phytoplasma diseases and their strains are being reported continuously, indicating that phytoplasmas are more diverse than previously thought. Phytoplasmas are mainly transmitted by insect vectors, such as leafhopper and planthopper, and can also be spread by grafting or Cuscuta australis (known as dodder). Mixed infections of phytoplasmas and viruses, bacteria, and spiroplasmas have also become a serious problem in several crops and are responsible for more synergistic losses. With the continuous development and improvement of technology, molecular biological detection has become the main technique for phytoplasma detection and identification. Currently, research on phytoplasma diseases in China mainly focuses on pathogen identification and classification, and insect vector and host diversity; however, there is less focus on pathogenicity, comparative genomics, and effect factors. More research attention has been paid to wheat blue dwarf phytoplasma, paulownia witches'-broom phytoplasma, jujube witches'-broom phytoplasma, and sugarcane white leaf phytoplasma. Other phytoplasma diseases have been reported; however, there have been no in-depth studies. In this paper, the history and present situation of phytoplasma research, and the status, distribution, and diversity of phytoplasma diseases are summarized, and some possible research directions of phytoplasma in the future in China are proposed.

With the rapid expansion of the Internet, it continuously penetrates the life of older adults around the world. This study aims to explore the effect of Internet use on the multi-dimensional health of the elderly with the mediating role of cultural engagement. Using data from the Chinese General Social Survey (CGSS) in 2015 and 2017, this study adopts logistic regression and a single-step multiple mediation model to investigate how Internet use affects the multi-dimensional health of older adults in China. The results show that Internet use has positive effects on the self-rated health, physical health, and mental health of the elderly. Endogenous tests, robustness analysis, and sensitivity analysis show that the above conclusions remain robust. Additionally, the mediating effect analysis shows that cultural engagement plays a mediating role in the relationship between Internet use and the three health-related responses. Therefore, to improve the elderly's health level, the government should not only cultivate the ability to use the Internet but also encourage greater cultural engagement amongst the aged.

Smart luminescent materials, which can respond to the changing of external environment (light, electricity, force, temperature, etc.), have always been one of the research hotspots. Mechanochromism refers to the materials whose emission color or intensity can be altered under the stimulation of external mechanical force. This kind of smart materials have been widely used in data storage, information encryption and sensors due to its simple operation, obvious and rapid response. The introduction of metal atoms in metal-organic compounds brings about fascinating metalophilic interactions and results in more interesting and surprising mechanochromic behaviors. In this mini-review, recent advances in mechanochromism of metal-organic compounds, including mono-, di-, multinuclear metal-organic complexes and metallic clusters are summarized. Varies mechanisms are discussed and some design strategies for metal-organic compounds with mechanochromism are also presented.

N6-methyladenosine (m6A) is the most common epigenetic modification of eukaryotic RNA, which can participate in the growth and development of the body and a variety of physiological and disease processes by affecting the splicing, processing, localization, transport, translation, and degradation of RNA. Increasing evidence shows that non-coding RNAs, particularly microRNA, long non-coding RNA, and circular RNA, can also regulate the RNA m6A modification process by affecting the expression of m6A-related enzymes. The interaction between m6A modification and non-coding RNAs provides a new perspective for the exploration of the potential mechanism of tumor genesis and development. In this review, we summarize the potential mechanisms and effects of m6A and non-coding RNAs in gastrointestinal tract cancers.

It remains poorly understood how brain causal connectivity networks change following hearing loss and their effects on cognition. In the current study, we investigated this issue. Twelve patients with long-term bilateral sensorineural hearing loss [mean age, 55.7 ± 2.0; range, 39–63 years; threshold of hearing level (HL): left ear, 49.0 ± 4.1 dB HL, range, 31.25–76.25 dB HL; right ear, 55.1 ± 7.1 dB HL, range, 35–115 dB HL; the duration of hearing loss, 16.67 ± 4.5, range, 3–55 years] and 12 matched normally hearing controls (mean age, 52.3 ± 1.8; range, 42–63 years; threshold of hearing level: left ear, 17.6 ± 1.3 dB HL, range, 11.25–26.25 dB HL; right ear, 19.7 ± 1.3 dB HL, range, 8.75–26.25 dB HL) participated in this experiment. We constructed and analyzed the causal connectivity networks based on functional magnetic resonance imaging data of these participants. Two-sample t-tests revealed significant changes of causal connections and nodal degrees in the right secondary visual cortex, associative visual cortex, right dorsolateral prefrontal cortex, left subgenual cortex, and the left cingulate cortex, as well as the shortest causal connectivity paths from the right secondary visual cortex to Broca’s area in hearing loss patients. Neuropsychological tests indicated that hearing loss patients presented significant cognitive decline. Pearson’s correlation analysis indicated that changes of nodal degrees and the shortest causal connectivity paths were significantly related with poor cognitive performances. We also found a cross-modal reorganization between associative visual cortex and auditory cortex in patients with hearing loss. Additionally, we noted that visual and auditory signals had different effects on neural activities of Broca’s area, respectively. These results suggest that changes in brain causal connectivity network are an important neuroimaging mark of cognitive decline. Our findings provide some implications for rehabilitation of hearing loss patients.

ObjectiveThis study reports a Chinese patient with a Congenital Disorder of Glycosylation (CDG) caused by compound-heterozygous mutations in the Conserved Oligomeric Golgi 5 (COG5) gene and thereby offers concrete evidence for early diagnosis.MethodsThe clinical manifestations, the results of laboratory examinations and genetic analysis of a 4-year-old Chinese girl with CDG are reported. We also reviewed previous CDG cases that involved COG5 mutations by comparing the phenotypes and genotypes in different cases.ResultsThe patient was admitted to our hospital due to ataxia and psychomotor delay. The major clinical manifestations were postural instability, difficulty in walking, psychomotor delay, hypohidrosis, hyperkeratosis of the skin, and ulnar deviation of the right-hand fingers. Biochemical analyses revealed coagulation defect and liver lesions. Vision tests showed choroidopathy and macular hypoplasia. Whole-exome sequencing identified the hitherto unreported compound-heterozygous COG5 mutations, c.1290C > A (p.Y430X) and c.2077A > C (p.T693P). Mutation p.Y430X is nonsense, leading to a truncated protein. Mutation p.T693P is located at a highly conserved region, and thus the polar-to-non-polar substitution presumably affects the structure and function of COG5. According to the Human Genome Mutation Database Professional, there have been totally 13 CDG cases caused by 13 COG5 mutations. They are mainly characterized by psychomotor delay, hypotonia, ataxia, microcephaly, and hearing and visual abnormalities.ConclusionThe clinical manifestations of the patient are mild but consistent with the clinical characteristics of the published COG5-CDG cases. The results of this study extend the spectrum of clinical and genetic findings in COG5-CDG.