Comprehensive Analysis of Immune Signatures in Primary Biliary Cholangitis and Autoimmune Hepatitis.

Primary Biliary Cholangitis (PBC) and Autoimmune Hepatitis (AIH) are autoimmune diseases that target hepatocytes and bile duct cells, respectively. Despite their shared autoimmune nature, the differences in immunologic characteristics between them remain largely unexplored. This study seeks to elucidate the unique immunological profiles of PBC and AIH, and to identify key differences. We comprehensively analyzed various T-cell subsets and their receptor expression in a cohort of 45 patients, including 27 PBC and 18 AIH cases. Both diseases exhibited T cell exhaustion and senescence along with a surge in inflammatory cytokines. Significantly increased CD38+HLA-DR+CD8+T cell populations were observed in both diseases. AIH was characterized by an upregulation of CD8+TEMRA, CD4+TEM, and CD4+TEMRA cells, and a concurrent reduction in Treg cells. In contrast, PBC displayed a pronounced presence of Tfh cells and a contraction of CD4-CD8-T cell populations. Correlation analysis revealed that NKP46+NK frequency was closely tied to ALT and AST levels, and TIGIT expression on T cells was associated with GLB level in AIH. In PBC, there is a significant correlation between Tfh cells and ALP levels. Moreover, the identified immune landscapes in both diseases strongly related to disease severity. Through logistic regression analysis, γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies emerged as distinct markers capable of differentiating PBC from AIH. In conclusion, our analyses reveal that PBC and AIH share similarities and differences regarding to immune profiles. And γδ T, TIGIT+Vδ2 T, and Tfh1 cell frequencies are potential noninvasive immunological markers that can differentiate PBC from AIH.

Ambient air pollution and the health-related quality of life of older adults: Evidence from Shandong China.

Ambient air pollution is a major public health concern impacting all aspects of human health. There is a lack of studies on the impact of ambient air pollution on health-related quality of life (HRQoL) of older Chinese adults. Our study answers two questions: How concentrations of ambient air pollutants are associated with HRQoL among older adults in China and, second, what are the possible mechanisms through which ambient air pollution affects HRQoL. From the 2018 National Health Service Survey, we sampled 5717 aged 65 years or older residents for the eastern province of Shandong, China. Data on individual exposures to PM2.5 and PM10 (particulate matter with diameter less than or equal to 2.5 µm and 10 µm) and sulfur dioxide (SO2) were collected from the ChinaHighAirPollutants (CHAP) datasets. Mixed-effects Tobit regression models and mixed-effects ordered Probit regression models were employed to examine the associations of long-term exposure to ambient air pollution with the European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) scale comprising mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Socioeconomic, demographic and behavioral factors relating to HRQoL were also examined. The results show that for each 1 µg/m3 increase, EQ-5D-3L scores fell 0.002 for PM2.5; 0.001 for PM10 and 0.002 for SO2. Long term exposure to PM2.5, PM10 and SO2 were also associated with increased prevalence of pain/discomfort and anxiety/depression. The reduced HRQoL effects of ambient air pollution were exacerbated by higher socioeconomic status (affluent, urban and higher level of education). Our findings suggested that HRQoL of older Chinese adults was not only associated with demographic, socioeconomic, and health-related factors, but also negatively correlated with air pollution, especially through increased pain/discomfort and anxiety/depression. The paper proposes policy recommendations.

First detection of the occurrence and study of the genetic diversity of novel putative kirkoviruses in donkey in China.

The first representative of a seemingly novel virus family has been found during the metagenomic examination of a diseased and dead horse in the USA [Li et al. in J Gen Virol 96:2721-2733, 2015]. These authors have suggested the need for the establishment of a new family with the tentative name Kirkoviridae; however, the suggested name is not official yet. Soon after the discovery, similar, relatively large CRESS-DNA viruses have been detected in various animals in China and elsewhere. Besides the two main genes (rep and cap), characteristic for members of the family Circoviridae, the tentative kirkoviruses have considerably larger genomes of approximately 4000 nucleotides. Accordingly, these viruses possess three four additional ORFs coding for proteins of unknown function. This has been described previously. In the present manuscript, the authors report the sequence of kirkovirus-like viruses, detected by PCR in donkey excretes in China. From 73 samples, 8 were found positive. From three of these newly detected viruses, the full genomic sequence was determined, whereas from the other five only one gene, namely the replication-associated (Rep) protein was sequenced.

Outbreak of neuropathogenic equid herpesvirus 1 causing abortions in Yili horses of Zhaosu, North Xinjiang, China.

BACKGROUND: EHV-1 is one of the most serious viral pathogens that frequently cause abortion in horses around the world. However, so far, relatively little information is available on EHV-1 infections as they occur in China. In January 2021, during an abortion storm which occurred in Yili horses at the Chinese State Studs of Zhaosu (North Xinjiang, China), 43 out of 800 pregnant mares aborted. RESULTS: PCR detection revealed the presence of EHV-1 in all samples as the possible cause of all abortions, although EHV-4, EHV-2 and EHV-5 were also found to circulate in the aborted fetuses. Furthermore, the partial ORF33 sequences of the 43 EHV-1 shared 99.3-100% and 99.0-100% similarity in nucleotide and amino acid sequences respectively. These sequences not only indicated a highly conserved region but also allowed the strains to group into six clusters. In addition, based on the predicted ORF30 nucleotide sequence, it was found that all the strains carried a guanine at the 2254 nucleotide position (aspartic acid at position 752 of the viral DNA polymerase) and were, therefore, identified as neuropathogenic strains. CONCLUSION: This study is the first one that establishes EHV-1 as the cause of abortions in Yili horses, of China. Further characterization of the ORF30 sequences revealed that all the EHV-1 strains from the study carried the neuropathogenic genotype. Totally, neuropathogenic EHV-1 infection in China's horse population should be concerned although the virus only detected in Yili horse abortions.

Ferroptosis in the tumor microenvironment: perspectives for immunotherapy.

Targeting ferroptosis, which provokes lipid peroxidation in cancer cells, presents potentially new avenues for anticancer therapy. Recent studies have begun to explore how immune cells in the tumor microenvironment (TME) respond and adapt to lethal lipid peroxides (LPOs). A better understanding of this process in the TME is likely to uncover another side of ferroptosis in cancer immunity and promote the development of ferroptosis-targeted therapy. This Opinion article overviews the main metabolic processes in ferroptosis, summarizes the emerging roles of ferroptosis not only in immune cells in the TME but also in the crosstalk between tumor cells and immune cells, and presents a perspective on the targeting of ferroptosis in cancer immunotherapy.

Simultaneously targeting SOAT1 and CPT1A ameliorates hepatocellular carcinoma by disrupting lipid homeostasis.

Lipid homeostasis plays a fundamental role in the development of hepatocellular carcinoma (HCC). However, the mechanisms that regulate lipid homeostasis to avoid lipotoxicity in HCC remain elusive. Here, we found high-fat diet (HFD) improved the expression of sterol o-acyltransferase1 (SOAT1) and carnitine palmitoyltransferase 1A (CPT1A) in diethylnitrosamine-induced HCC. Bioinformatic analysis showed that SOAT1-mediated fatty acid storage and CPT1A-mediated fatty acids oxidation (FAO) formed a double-negative feedback loop in HCC. We verified that SOAT1 inhibition enhanced CPT1A protein, which shuttled the released fatty acids into the mitochondria for oxidation in vivo and in vitro. Besides, we further confirmed that CPT1A inhibition converted excess fatty acids into lipid drops by SOAT1 in vitro. Simultaneously targeting SOAT1 and CPT1A by the small-molecule inhibitors avasimibe and etomoxir had synergistic anticancer efficacy in HCC in vitro and in vivo. Our study provides new mechanistic insights into the regulation of lipid homeostasis and suggests the combination of avasimibe and etomoxir is a novel strategy for HCC treatment.

Identification and genomic characterization of emerging CRESS DNA viruses in thoroughbred horses in China.

Multiple novel circular replication-associated protein (Rep)-encoding single stranded (CRESS) DNA viruses have been extensively identified in the feces of humans and animals. Here, we first detected CRESS DNA virus (named Horse-CRESS DNA-like virus, HCLV) in two fecal samples from 10 imported thoroughbred (TB) horses in the customs quarantine station in North Xinjiang province, China. Additionally, we found that this virus was not detected in local breeds (LBs) (0/41) and was found only in imported TB horses (2/73). We obtained the whole-genome sequences of four viruses (HCLV ALSK-3-4, ALSK-13-10, CJ-1-2, and CJ-13-1). Unlike Circovirus and Cyclovirus, whose genome sequences have 1700 to 2100 nucleotides (nt), these HCLVs have circular genome with 3503, 3504, 3485, 3491 nt, respectively and five major ORFs. The ORF1 gene encodes the Rep protein in HCLVs. Furthermore, the Rep protein of the four HCLVs share 23.3-84.8%, 21.6-27.4%, 23.7-27.2% amino acid identity with the corresponding reference viruses of Kirkoviruses, genus Circovirus, and genus Cyclovirus, respectively. Moreover, RCR domain, P-loop NTPase domains, and nonanucleotide motif (TAGTATTAC) of the HCLVs are similar to Circovirus and Cyclovirus. Phylogenetic analysis showed that the virus was grouped together with members in Kirkoviruses. These results suggest the HCLV probably entered Xinjiang province via the international trade of horses.

First detection and genetic characterization of equid herpesvirus 2, 4, and 5 in China.

In November 2018, an outbreak of respiratory disease occurred in foals at an equestrian club in Changji, northern Xinjiang, China. We applied viral metagenomics to investigate this outbreak and identify potential pathogens involved in this equine respiratory syndrome. The metagenomics data revealed the presence of sequences matching those of equid herpesvirus (EHV) 2, 4, and 5. PCR with specific primers targeting ORF33 of EHV-4 and ORF8 of EHV-2 and EHV-5 revealed coinfection with these viruses in this respiratory syndrome. To investigate the prevalence of these viruses in China, 453 nasal swabs from clinically healthy thoroughbred foals (36/453, 7.9%) and horses (417/453, 92.1%) were collected from several equestrian clubs. Forty-five (9.9%) of the samples tested positive for EHV-5 DNA, and seven (1.5%) tested positive for EHV-2, but all were negative for EHV-4 DNA. Forty-nine (10.8%) samples tested positive for both EHV-5 and EHV-2 DNA. Using these samples, one complete EHV-4 ORF33, 10 partial EHV-2 ORF8, and 50 partial EHV-5 ORF8 sequences from the 10 diseased foals and 50 thoroughbred horses were then determined. Sequence analysis indicated that EHV-4 ORF33 and EHV-5 ORF8, in contrast to EHV-2 ORF8, had high sequence similarity to those of published sequences. Our data provide the first evidence that EHV-2, -4, and -5 co-circulate in China and that EHV-4 is potentially involved in this respiratory disease in foals.

Effects of massage therapy for patients with thoracic facet joint disorders: A protocol for systematic review and meta-analysis.

BACKGROUND: Thoracic facet joint disorder is a common thoracic disorder in clinic, inducing pain and discomfort at the dislocated thoracic vertebrae, radiating to pain of the neck and back. The incidence of thoracic facet joint disorder is higher than the facet disorder of the cervical and lumbar vertebrae. Therefore, an ideal strategy to relieve thoracic facet joint disorder is urgently needed. In recent years, massage therapy has been increasingly accepted by thoracic facet joint disorder patients due to its lower costs, fewer unwanted side effects and safety for clinical use. In this systematic review, we aim to evaluate the effectiveness and safety of massage therapy for patients with thoracic facet joint disorder. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness of massage therapy in treating thoracic facet joint disorder: Wanfang and PubMed Database, CNKI, CENTRAL, CINAHL and EMBASE. Each database will be searched from inception to October 2020. The entire process will include study selection, data extraction, risk of bias assessment and meta-analyses. RESULTS: This proposed study will evaluate the effectiveness of massage therapy for patients with thoracic facet joint disorder. CONCLUSIONS: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with thoracic facet joint disorder. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/XMEJD.

Effects and safety of massage therapy for patients with metatarsal pain: A protocol for systematic review and meta-analysis.

BACKGROUND: Metatarsalgia refers to localized or generalized forefoot pain in the region of the metatarsal heads. Often this pain is plantar, beneath the metatarsal heads, and arises from either mechanical or iatrogenic causes. The treatment of metatarsalgia remains controversial. A thorough understanding of the biomechanics of the forefoot and the underlying pathology of the particular type of metatarsalgia affecting the patient is a prerequisite to selecting the proper treatment. In recent years, massage therapy has been increasingly accepted by patients due to its lower costs, fewer unwanted side effects, and safety for clinical use. In this systematic review, we aim to evaluate the effectiveness and safety of massage therapy for patients with metatarsal pain. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating metatarsal pain: Wanfang and PubMed Database, CNKI, CENTRAL, CINAHL, and EMBASE. Each database will be searched from inception to October 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULTS: This proposed study will evaluate the effectiveness and safety of massage therapy for patients with metatarsal pain. The outcomes will include changes in metatarsal pain relief and adverse effect. CONCLUSIONS: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with metatarsalgia. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/C6KFJ.

[Research on Breeding of the New Rehmannia glutinosa Variety].

Objective: To breed new Rehmannia glutinosa varieties with best comprehensive properties. Methods: By space mutation of hybrid seeds of 85-5 and Beijing No. 1,after systemic breeding, Huaidi 81 with excellent comprehensive characters was screened. Fresh weight, benchmark composition content, resistance, chlorophyll and anthocyanin content, photosynthetic characteristics of the new variety and the main cultivars were determined. Results: Per plant fresh weight of Huaidi 81 was higher than those five main varieties and there was extremely significant difference between Huaidi 81 and other varieties,the yield of Huaidi 81( 82 353 kg / hm2) was29. 7% higher than that 5 main varieties. The catalpol content of different Rehmannia glutinosa varieties ranked in the order as follows, Beijing No. 3( 1. 601%) > Qinhuai( 1. 588%) > Huaidi 81( 1. 314%) > Godden nine > 85-5( 1. 073%) > Huaifeng( 0. 924%),the catalpol content of Huaidi 81 was in the middle, and there was no significant difference between Huaidi 81 and Godden nine,but extremely significant difference from other varieties. The acteoside content of different Rehmannia glutinosa varieties ranked in the order as follows,Huaidi 81( 0. 096%) > Qin Huai( 0. 069%) > 85-5( 0. 047%) > Beijing No. 3( 0. 035%) > Huaifeng( 0. 023%) > Golden nine( 0. 022%),the content of acteoside of Huaidi 81 was higher than those five main varieties, and there was extremely significant difference between Huaidi 81 and other varieties. Huaidi 81 had high resistance to Septoris digitalis, and had middle resistance to leaf ring rot, which indicated that Huaidi 81 had good resistance to leaf disease. Huaidi 81 with the highest chlorophyll content and moderate anthocyanin content, and had the highest photosynthetic rate. Conclusion: The new variety Huaidi 81 with best comprehensive properties is suitable for popularizing as a new Rehmannia glutinosa variety.

Detection of aflatoxin B1 with immunochromatographic test strips: Enhanced signal sensitivity using gold nanoflowers.

Immunochromatographic test strips (ICTS) are commonly limited to higher concentrations of analytes. This limitation stems from the relatively low sensitivity of conventional gold nanospheres (AuNSs with a diameter of 20 nm) to emit detectable brightness values. The larger multi-branched gold nanoflowers (AuNFs) with a higher optical brightness as well as good colloidal stability exhibit significant improvements over conventional AuNSs for enhanced sensitivity of ICTS. In this study, blue AuNFs with an average diameter of 75±5 nm were synthetized and employed as a signal amplification probe for ultrasensitive and quantitative detection of aflatoxin B1 (AFB1) in rice. A portable optical strip reader was used to record the optical densities of test and control lines of the strip. Under the optimal conditions, the AuNF based ICTS system accurately detected AFB1 linearly and dynamically over the range of 0.5-25 pg/mL with a half maximal inhibitory concentration at 4.17 pg/mL. The inhibitory concentration was achieved 10 times lower than that of the traditional AuNS based ICTS systems (41.25 pg/mL). The limit of detection for AFB1 in rice extract was achieved at 0.32 pg/mL. In summary, AuNFs are a novel probe that exhibited excellent sensitivity in the ICTS system and could be used for ultrasensitive detection of other analytes in food safety monitoring, and even medical diagnostics.

[Research on Breeding of Dioscorea opposita cv. Tiegun].

OBJECTIVE: To breeding the new varieties Dioscorea opposita cv. Tiegun with the best comprehensive properties. METHODS: Seven new Dioscorea opposita. cv. Tiegun cultivars were screened by space mutation breeding of Dioscorea opposita cv. Tiegun bulbils. Yield,allantoin content,water soluble extractive and the resistance of these seven cultivars were compared with the main cultivar Dioscorea opposita cv. Tiegun( CK). Meanwhile, the nutrition quality of new cultivars No. 6 and No. 10 were compared with the main cultivar. RESULTS: (1) The fresh weight per plant ranked in the order as follows: No. 6 > No. 10 > No. 4 > No. 9 > No. 1 > CK > No. 2 > No. 8. The drying rate ranked in the order as follows: No. 2 > No. 10 > No. 9 > No. 6 > No. 8 > CK > No. 1 > No. 4. Dry weight per plant ranked in the order as follows: No. 10 > No. 9 > No. 6 > No. 2 > No. 1 > CK > No. 4 > No. 8. The fresh weight per plant, drying rate and dry weight per plant of No. 6 and No. 10 were higher than the main cultivar. (2) The allantoin content ranked in the order as follows: No. 6 > No. 4 > No. 10 > CK > No. 9 > No. 8 > No. 2 > No. 1. (3) The water soluble extractive contents ranked in the order as follows: No. 6 > No. 2 > No. 4 > No. 10 > No. 1 > CK > No. 9 > No. 8. The water soluble extractive content of No. 6 was higher than No. 10 and the main cultivar. (4) No. 10 had the best taste of dry, soft, sweet and fragrant, No. 6 had the taste of dry, floury and hard, and No. 9 had the taste of dry and crisp. (5) No. 6 had the strongest resistance to Gloeosporium pestis and Cykindrosporium dioscoreae; No. 10 had a middle resistance to Gloeosporium pestis and a strong resistance to Cykindrosporium dioscoreae; and the main cultivar had a middle degree of being prone to Gloeosporium pestis and a middle resistance to Cykindrosporium dioscoreae. (6) The content of starch, reducing sugar, protein and ash in No. 6 and No. 10 were higher than that of the main cultivar,while the content of water in No. 6 and No. 10 were lower,which indicated that the nutrition quality of No. 6 and No. 10 is better than the main cultivar. CONCLUSION: The new cultivar No. 10 is suitable for popularizing as a new variety of edible Dioscorea opposita cv. Tiegun. The new cultivar No. 6 is suitable for popularizing as a new variety of medicinal Dioscorea opposita cv. Tiegun.

Immunochromatographic assay for ultrasensitive detection of aflatoxin B1 in maize by highly luminescent quantum dot beads.

Highly luminescent quantum dot beads (QBs) were synthesized by encapsulating CdSe/ZnS and used for the first time as immunochromatographic assay (ICA) signal amplification probe for ultrasensitive detection of aflatoxin B1 (AFB1) in maize. The challenges to using high brightness QBs as probes for ICA are smooth flow of QBs and nonspecific binding on nitrocellulose (NC) membrane, which are overcome by unique polymer encapsulation of quantum dots (QDs) and surface blocking method. Under optimal conditions, the QB-based ICA (QB-ICA) sensor exhibited dynamic linear detection of AFB1 in maize extract from 5 to 60 pg mL(-1), with a median inhibitory concentration (IC50) of 13.87 ± 0.16 pg mL(-1), that is significantly (39-fold) lower than those of the QD as a signal probe (IC50 = 0.54 ± 0.06 ng mL(-1)). The limit of detection (LOD) for AFB1 using QB-ICA sensor was 0.42 pg mL(-1) in maize extract, which is approximately 2 orders of magnitude better than those of previously reported gold nanoparticle based immunochromatographic assay (AuNP-ICA) and is even comparable with or better than the conventional enzyme-linked immunosorbent assay (ELISA) method. The performance and practicability of our QB-ICA sensor were validated with a commercial ELISA kit and further confirmed with liquid chromatography tandem mass spectrometry (LC-MS/MS). Given its efficient signal amplification performance, the proposed QB-ICA offers great potential for rapid, sensitive, and cost-effective quantitative detection of analytes in food safety monitoring.