Molecular detection and genetic characteristics of porcine circovirus 3 and porcine circovirus 4 in central China.

Porcine circoviruses (PCVs) are a significant cause of concern for swine health, with four genotypes currently recognized. Two of these, PCV3 and PCV4, have been detected in pigs across all age groups, in both healthy and diseased animals. These viruses have been associated with various clinical manifestations, including porcine dermatitis and nephropathy syndrome (PDNS) and respiratory and enteric signs. In this study, we detected PCV3 and PCV4 in central China between January 2022 and February 2023. We tested fecal swabs and tissue samples from growing-finishing and suckling pigs with or without respiratory and systemic manifestations and found the prevalence of PCV3 to be 15.15% (15/99) and that of PCV3/PCV4 coinfection to be 4.04% (4/99). This relatively low prevalence might be attributed to the fact that most of the clinical samples were collected from pigs exhibiting respiratory signs, with only a few samples having been obtained from pigs with diarrhea. In some cases, PCV2 was also detected, and the coinfection rates of PCV2/3, PCV2/4, and PCV2/3/4 were 6.06% (6/99), 5.05% (5/99), and 3.03% (3/99), respectively. The complete genomic sequences of four PCV3 and two PCV4 isolates were determined. All four of the PCV3 isolates were of subtype PCV3b, and the two PCV4 isolates were of subtype PCV4b. Two mutations (A24V and R27K) were found in antibody recognition domains of PCV3, suggesting that they might be associated with immune escape. This study provides valuable insights into the molecular epidemiology and evolution of PCV3 and PCV4 that will be useful in future investigations of genotyping, immunogenicity, and immune evasion strategies.

DJ-1 protects cell death from a mitochondrial oxidative stress due to GBA1 deficiency.

BACKGROUND: GBA1 mutations are the most common genetic risk factor for development of Parkinson's disease (PD). The loss of catalytic activity in GBA1, as well as the reduction of the GBA1 protein in certain cellular compartment, may increase disease progression. However, the mechanisms underlying cellular dysfunction caused by GBA1 deficiency are still mostly unknown. OBJECTIVE: In this study, we focus on the genetic interaction between GBA1 deficiency and PD-causing genes, such as DJ-1, in mitochondrial dysfunction. METHODS: GBA1 knockout (KO) SH-SY5Y cells were used to assess DJ-1 functions against oxidative stress in vitro. The levels of cellular reactive oxygen species were monitored with MitoSOX reagent. The expression of the PARK7 gene was analyzed using the quantitative real-time PCR (qRT-PCR). To understand the mechanism underlying DJ-1 upregulation in GBA1 KO cells, we assess ROS levels, antioxidant protein, and cell viability in GBA1 KO cells with treatment of ROS inhibitor N-acetyl-cysteine or miglustat, which is an inhibitor of glucosylceramide synthase. Dopaminergic degeneration was assessed from Gba1 L444P heterozygous mice mated with Park7 knockout mice. RESULTS: We find that DJ-1 is significantly upregulated in GBA1 KO cells. Elevated levels of DJ-1 are attributed to the transcriptional expression of PARK7 mRNA, but not the inhibition of DJ-1 protein degradation. Because DJ-1 expression is highly linked to oxidative stress, we observe cellular reactive oxygen species (ROS) in GBA1 KO cells. Moreover, several antioxidant gene expressions and protein levels are increased in GBA1 KO cells. To this end, GBA1 KO cells are more susceptible to H2O2-induced cell death. Importantly, there is a significant reduction in dopaminergic neurons in the midbrain from Gba1 L444P heterozygous mice mated with Park7 knockout mice, followed by mild motor dysfunction. CONCLUSION: Taken together, our results suggest that DJ-1 upregulation due to GBA1 deficiency has a protective role against oxidative stress. It may be supposed that mutations or malfunctions in the DJ-1 protein may have disadvantages in the survival of dopaminergic neurons in the brains of patients harboring GBA1 mutations.

Antioxidant Defenses Against Air Humidity Stress in Fruit Bodies of Auricularia heimuer (Agaricomycetes).

Air humidity is an important environmental factor restricting the fruit body growth of Auricularia heimuer. Low air humidity causes the fruit body to desiccate and enter dormancy. However, the survival mechanisms to low air humidity for fruit bodies before dormancy remain poorly understood. In the present study, we cultivated A. heimuer in a greenhouse and collected the fruit bodies at different air humidities (90%, 80%, 70%, 60%, and 50%) to determine the contents of malondialdehyde (MDA) and non-enzymatic antioxidants such as ascorbic acid (AsA) and glutathione (GSH); and the activities of enzymatic antioxidants including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX) and glutathione reductase (GR). Results showed that the MDA contents tended to increase with decreasing relative air humidity. Relative air humidity below 90% caused membrane lipid peroxidation and oxidative stress (based on MDA contents) to the fruit body, which we named air humidity stress. In contrast to the control and with the degree of stress, the GSH contents and activities of SOD, CAT, GR, GPX, and APX tended to ascend, whereas AsA showed a declining trend; the POD activity only rose at 50%. The antioxidants favored the fruit body to alleviate oxidative damage and strengthened its tolerance to air humidity stress. The antioxidant defense system could be an important mechanism for the fruit body of A. heimuer in air humidity stress.

Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis.

BACKGROUND: The systemic inflammatory response index (SIRI) has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms. However, research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer surgery. AIM: To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients, who received robotic radical gastric cancer surgery. METHODS: Initially, an exhaustive retrieval was performed in the PubMed, the Cochrane Library, EMBASE, Web of Science, and Scopus databases to identify relevant studies. Subsequently, a meta-analysis was executed on 6 cohort studies identifying the value of the SIRI in assessing the survival of gastric cancer patients. Additionally, the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators. The association between preoperative SIRI levels and 5-year overall survival (OS) and disease-free survival (DFS) was assessed. RESULTS: The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer. Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer. SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities, T-stage, carcinoembryonic antigen levels, the development of early serious postoperative complications, and the rate of lymph node metastasis. CONCLUSION: SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents.

Novel psychoactive substances (NPSs) are new psychotropic drugs designed to evade substance regulatory policies. 25E-NBOMe (2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) has recently been identified as an NPS, and its recreational misuse has been reported to be rapidly increasing. However, the psychopharmacological effects and mechanisms of 25E-NBOMe have not been studied. We examined the abuse potential of 25E-NBOMe using the conditioned place preference in male mice and self-administration paradigms in male rats. Additionally, immunoblot assay, enzyme-linked immunosorbent assay, and microdialysis were used to determine the molecular effects of 25E-NBOMe in the nucleus accumbens (NAc). Our data demonstrated that 25E-NBOMe induces conditioned place preference, and the dopaminergic signaling in the NAc mediates these. Following 25E-NBOMe administration, expression of dopamine transporter and dopamine D1 receptor (D1DR) were enhanced in the NAc of male mice, and NAc dopamine levels were reduced in both male mice and rats. Induction of intracellular dopaminergic pathways, DARPP32, and phosphorylation of CREB in the NAc of male mice was also observed. Significantly, pharmacological blockade of D1DR or chemogenetic inhibition of D1DR-expressing medium spiny neurons in the NAc attenuated 25E-NBOMe-induced conditioned place preference in male mice. We also examined the hallucinogenic properties of 25E-NBOMe using the head twitch response test in male mice and found that this behavior was mediated by serotonin 2A receptor activity. Our findings demonstrate that D1DR signaling may govern the addictive potential of 25E-NBOMe. Moreover, our study provides new insights into the potential mechanisms of substance use disorder and the improvement of controlled substance management.

Arctigenin Induces Apoptosis in Melanoma Cells by Reducing the Expression of BCL-2 and VEGF.

BACKGROUND: To investigate the biological effects of arctigenin on B16-F10 melanoma cells in vitro and to explore its mechanism. METHODS: B16-F10 melanoma cells in vitro were treated with the blank control solution and arctigenin solution of different concentrations, respectively. Cell proliferation and apoptosis were analyzed using the CCK-8 assay and cell loss assay, and the effect of arctigenin on melanoma cell proliferation was evaluated. Western blot was used to analyze the expression of BCL-2 protein and vascular endothelial growth factor (VEGF) in the cells of different groups and to explore the mechanism of action of arctigenin. RESULTS: The proliferation rate of B16-F10 melanoma cells treated with arctigenin solutions was significantly lower than that of the blank control group (P < .05), and the proliferation rate decreased with increasing concentration of arctigenin. The apoptosis rate of B16-F10 melanoma cells treated with arctigenin solutions was significantly higher than that of the blank control group (P < .05), and the apoptosis rate increased with increasing concentration of arctigenin. The expression levels of BCL-2 and VEGF in B16-F10 melanoma cells treated with arctigenin solutions were significantly lower than those in the blank control group (P < .05), and the expression levels decreased as the concentration of arctigenin increased. CONCLUSIONS: Arctigenin can inhibit the proliferation and promote the apoptosis of melanoma cells, and the mechanism may be associated with decreasing the expression of BCL-2 and VEGF in melanoma cells.

Activation of autophagy promotes the inhibitory effect of curcumin analog EF-24 against MDA-MB-231 cancer cells.

Breast cancer is the leading cause of cancer deaths in women worldwide. EF-24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF-24 against one breast cancer cell line, MDA-MB-231, and its anti-migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF-24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF-24 also induced mitochondrial apoptosis in MDA-MB-231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3-MA could reduce the cleavage of PARP protein and protect cells from EF-24-induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF-24 in MDA-MB-231 cells, which suggest that EF-24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF-24 in breast cancer cells. Moreover, removal of EF-24-activated ROS with NAC significantly reversed migration ability of MDA-MB-231 cells, indicating that EF-24 exerted an inhibitory effect through a ROS-mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.

First detection of Candidatus Rickettsia tarasevichiae in Hyalomma marginatum ticks.

Ticks are important vectors of zoonotic diseases and play a major role in the circulation and transmission of many rickettsial species. The aim of this study was to investigate the carriage of Candidatus Rickettsia tarasevichiae (CRT) in a total of 1168 ticks collected in Inner Mongolia to elucidate the potential public health risk of this pathogen, provide a basis for infectious disease prevention, control and prediction and contribute diagnostic ideas for clinical diseases that present with fever in populations exposed to ticks. A total of four tick species, Haemaphysalis concinna (n = 21), Dermacentor nuttalli (n = 122), Hyalomma marginatum (n = 148), and Ixodes persulcatus (n = 877), were collected at nine sampling sites in Inner Mongolia, China, and identified by morphological and molecular biological methods. Reverse transcription PCR targeting the 16S ribosomal RNA (rrs), gltA, groEL, ompB and Sca4 genes was used to detect CRT DNA. Sequencing was used for pathogen species confirmation. The molecular epidemiological analysis showed that three species of ticks were infected with CRT, and the overall positive rate was as high as 42%. The positive rate of I. persulcatus collected in Hinggan League city was up to 96%, and that of I. persulcatus collected in Hulun Buir city was 50%. The pool positive rates of D. nuttalli and H. marginatum collected in Bayan Nur city and H. concinna collected in Hulun Buir city were 0%, 28% and 40%, respectively. This study revealed the high prevalence of CRT infection in ticks from Inner Mongolia and the first confirmation of CRT detected in H. marginatum in China. The wide host range and high infection rate in Inner Mongolia may dramatically increase the exposure of CRT to humans and other vertebrates. The role of H. marginatum in the transmission of rickettsiosis and its potential risk to public health should be further considered.

Chinese patent medicine as a complementary and alternative therapy for type 2 diabetes mellitus: A scoping review.

OBJECTIVE: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients' health outcomes, and set priorities in addressing research gaps in this area. METHODS: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. RESULTS: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). CONCLUSION: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

A Method for the Synthesis of Thioindoles through Copper-Catalyzed C-S Bond Coupling Reaction.

We herein report the copper-catalyzed C-S bond coupling reaction of indoles with N-thiosuccinimides, resulting in moderate to excellent yields of mono- and bis-sulfenylated compounds such as arylthioindoles, alkylthioindoles, selenylated indoles, and cysteine-substituted indoles. Thioarylation and thioglycosylation at the C2 position of indole alkaloids in the Radix Isatidis were achieved via structural modification. The first total syntheses of isatindigotindolosides III and IV have been successfully carried out. The electrophilic sulfenyl bromides generated in situ can play an important role in the catalytic cycle.

P450-Modified Ribosomally Synthesized Peptides with Aromatic Cross-Links.

Cyclization of linear peptides is an effective strategy to convert flexible molecules into rigid compounds, which is of great significance for enhancing the peptide stability and bioactivity. Despite significant advances in the past few decades, Nature and chemists' ability to macrocyclize linear peptides is still quite limited. P450 enzymes have been reported to catalyze macrocyclization of peptides through cross-linkers between aromatic amino acids with only three examples. Herein, we developed an efficient workflow for the identification of P450-modified RiPPs in bacterial genomes, resulting in the discovery of a large number of P450-modified RiPP gene clusters. Combined with subsequent expression and structural characterization of the products, we have identified 11 novel P450-modified RiPPs with different cross-linking patterns from four distinct classes. Our results greatly expand the structural diversity of P450-modified RiPPs and provide new insights and enzymatic tools for the production of cyclic peptides.

Effect of electroacupuncture at the acupoints for Tiaozang Xingshen on cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction. / "调脏醒神"电针对2åž‹ç³–å°¿ç— ç›¸å ³è®¤çŸ¥åŠŸèƒ½éšœç¢æ‚£è€ è„‘å† ä»£è°¢çš„å½±å“.

OBJECTIVES: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. METHODS: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. RESULTS: Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). CONCLUSIONS: Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.

Microbial diversity of ticks and a novel typhus group Rickettsia species (Rickettsiales bacterium Ac37b) in Inner Mongolia, China.

Ticks can carry multiple pathogens, and Inner Mongolia's animal husbandry provides excellent environmental conditions for ticks. This study characterized the microbiome of ticks from different geographical locations in Inner Mongolia; 905 Dermacentor nuttalli and 36 Ixodes persulcatus were collected from sheep in three main pasture areas and from bushes within the forested area. Mixed DNA samples were prepared from three specimens from each region and tick species. Microbial diversity was analyzed by 16S rRNA sequencing, and α and ß diversity were determined. The predominant bacterial genera were Rickettsia (54.60%), including Rickettsiales bacterium Ac37b (19.33%) and other Rickettsia (35.27%), Arsenophonus (11.21%), Candidatus Lariskella (10.84%), and Acinetobacter (7.17%). Rickettsia bellii was identified in I. persulcatus, while Rickettsiales bacterium Ac37b was found in D. nuttalli from Ordos and Chifeng. Potential Rickettsia and Anaplasma coinfections were observed in the Ordos region. Tick microbial diversity analysis in Inner Mongolia suggests that sheep at the sampling sites were exposed to multiple pathogens.

Title: Diversité microbienne des tiques et nouvelle espèce de Rickettsia du groupe du typhus (bactérie Rickettsiales Ac37b) en Mongolie intérieure, Chine. Abstract: Les tiques peuvent être porteuses de plusieurs agents pathogènes et l'élevage en Mongolie intérieure offre d'excellentes conditions environnementales pour les tiques. Cette étude a caractérisé le microbiome des tiques de différentes zones géographiques de Mongolie intérieure; 905 Dermacentor nuttalli et 36 Ixodes persulcatus ont été collectés sur des moutons dans trois principales zones de pâturage et dans des buissons de la zone forestière. Des échantillons d'ADN mixtes ont été préparés à partir de trois spécimens de chaque région et espèce de tique. La diversité microbienne a été analysée par séquençage de l'ARNr 16S et la diversité α et ß a été déterminée. Les genres bactériens prédominants étaient les Rickettsia (54,60 %), dont la bactérie Rickettsiales Ac37b (19,33 %) et d'autres Rickettsia (35,27 %), Arsenophonus (11,21 %), Candidatus Lariskella (10,84 %) et Acinetobacter (7,17 %). Rickettsia bellii a été identifiée chez I. persulcatus, tandis que la bactérie Rickettsiales Ac37b a été trouvée chez D. nuttalli d'Ordos et Chifeng. Des co-infections potentielles à Rickettsia et Anaplasma ont été observées dans la région d'Ordos. L'analyse de la diversité microbienne des tiques en Mongolie intérieure montre que les moutons présents sur les sites d'échantillonnage sont exposés à plusieurs agents pathogènes.

Quantum-noise-limited optical neural networks operating at a few quanta per activation.

A practical limit to energy efficiency in computation is ultimately from noise, with quantum noise [1] as the fundamental floor. Analog physical neural networks [2], which hold promise for improved energy efficiency and speed compared to digital electronic neural networks, are nevertheless typically operated in a relatively high-power regime so that the signal-to-noise ratio (SNR) is large (>10). We study optical neural networks [3] operated in the limit where all layers except the last use only a single photon to cause a neuron activation. In this regime, activations are dominated by quantum noise from the fundamentally probabilistic nature of single-photon detection. We show that it is possible to perform accurate machine-learning inference in spite of the extremely high noise (signal-to-noise ratio ~ 1). We experimentally demonstrated MNIST handwritten-digit classification with a test accuracy of 98% using an optical neural network with a hidden layer operating in the single-photon regime; the optical energy used to perform the classification corresponds to 0.008 photons per multiply-accumulate (MAC) operation, which is equivalent to 0.003 attojoules of optical energy per MAC. Our experiment also used >40× fewer photons per inference than previous state-of-the-art low-optical-energy demonstrations [4, 5] to achieve the same accuracy of >90%. Our training approach, which directly models the system's stochastic behavior, might also prove useful with non-optical ultra-low-power hardware.

Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling.

Considerable achievements were realized in illuminating underlying pathological mechanisms of patients with idiopathic membranous nephropathy (IMN). Although IMN patients are well diagnosed before they reach renal failure, no currently available drug intervention is effective in halting IMN progression. In this study, we assess Moshen granule (MSG) effect on IMN patients and cationic bovine serum albumin (CBSA)-induced rats. Increasing studies has indicated that activation of aryl hydrocarbon receptor (AHR) was related to oxidative stress and inflammation. We further determine MSG effect on AHR, nuclear factor ƙB (NF-ƙB) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the CBSA-induced rats. MSG markedly reduces proteinuria and improves kidney function in both IMN patients and rats induced by CBSA. MSG markedly inhibits increased mRNA expressions of intrarenal AHR and its four downstream target genes including CYP1A1, CYP1A2, CYP1B1 and COX-2 compared with untreated CBSA-induced rats. This is accompanied by markedly downregulated protein expressions of p-IƙBα and NF-ƙB p65 and its downstream gene products including MCP-1, COX-2, 12-LOX, iNOS, p47phox and p67phox, while markedly preserves protein expressions of Nrf2 and its downstream gene products including catalase, HO-1, GCLM, GCLC, MnSOD and NQO1 in the kidney tissues. These data suggests MSG blunts podocyte damage through inhibiting activation of NF-ƙB/Nrf2 pathway via AHR signaling. This finding may provide a promising therapy for treatment of IMN through oxidative stress and inflammation.

Linking Gba1 E326K mutation to microglia activation and mild age-dependent dopaminergic Neurodegeneration.

Mutations in the GBA1 gene have been identified as a prevalent genetic risk factor for Parkinson's disease (PD). GBA1 mutations impair enzymatic activity, leading to lysosomal dysfunction and elevated levels of α-synuclein (α-syn). While most research has primarily focused on GBA1's role in promoting synucleinopathy, emerging evidence suggests that neuroinflammation may be a key pathogenic alteration caused by GBA1 deficiency. To examine the molecular mechanism underlying GBA1 deficiency-mediated neuroinflammation, we generated Gba1 E326K knock-in (KI) mice using the CRISPR/Cas9 technology, which is linked to an increased risk of PD and dementia with Lewy bodies (DLB). In the ventral midbrain and hippocampus of 24-month-old Gba1 E326K KI mice, we found a moderate decline in GBA1 enzymatic activity, a buildup of glucosylceramide, and an increase in microglia density. Furthermore, we observed increased levels of pro-inflammatory cytokines and formation of reactive astrocytes in primary microglia and astrocytes, respectively, cultured from Gba1 E326K KI mice following treatment with pathologic α-syn preformed fibrils (PFF). Additionally, the gut inoculation of α-syn PFF in Gba1 E326K KI mice significantly enhanced the accumulation of Lewy bodies in the dentate gyrus of the hippocampus, accompanied by aggravated neuroinflammation and exacerbated non-motor symptoms. This research significantly enhances our understanding of the Gba1 E326K mutation's involvement in neuroinflammation and the cell-to-cell transmission of pathogenic α-syn in the brain, thereby opening new therapeutic avenues.

Characterization of a gE/gI/TK gene-deleted pseudorabies virus variant expressing the Cap protein of porcine circovirus type 2d.

Porcine circovirus type 2 (PCV2) plays a key role in the etiology of PCV2-associated disease (PCVAD), and its predominant strain is PCV2d which is not completely controlled by most commercially available vaccines against PCV2a strains. Pseudorabies (PR) caused by pseudorabies virus (PRV) variants re-emerged in Bartha-K61 vaccine-immunized swine herds in late 2011, which brought considerable losses to the global pig husbandry. Therefore, it is significantly important to develop a safe and effective vaccine against both PCV2d and PRV infection. In the present study, the PCV2d ORF2 gene was amplified by PCR, and cloned into the BamHI site of PRV transfer plasmid pG vector to obtain the recombinant transfer plasmid pG-PCV2dCap-EGFP. Subsequently, it was transfected into ST cells infected with the three gene deleted PRV variant strain NY-gE-/gI-/TK- to generate a recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+/EGFP+, and then the EGFP gene was knocked out to harvest the rPRV NY-gE-/gI-/TK-/PCV2dCap+ using gene-editing technology termed CRISPR/Cas9 system. The recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+ had similar genetic stability and proliferation characteristics to the parental PRV as indicated by PCR and one-step growth curve test, and the expression of Cap was validated by Western blot. In animal experiment, higher PCV2-specific ELISA antibodies and detectable PCV2-specific neutralizing antibodies could be elicited in mice immunized with rPRV NY-gE-/gI-/TK-/PCV2dCap+ compared to commercial PCV2 inactivated vaccine. Moreover, the recombinant virus rPRV NY-gE-/gI-/TK-/PCV2dCap+ significantly reduced the viral loads in the hearts, livers, spleens, lungs, and kidneys in mice following a virulent PCV2d challenge. Mice immunized with rPRV NY-gE-/gI-/TK-/PCV2dCap+ developed comparable PRV-specific humoral immune responses and provided complete protection against a lethal PRV challenge. Together, the rPRV NY-gE-/gI-/TK-/PCV2dCap+ recombinant strain has strong immunogenicity.

Molecular detection and genetic characteristics of a novel porcine circovirus (porcine circovirus 4) and porcine reproductive and respiratory syndrome virus in Shaanxi and Henan Provinces of China.

Porcine circovirus 4 (PCV4) is a recently discovered circovirus that was first reported in 2019 in several pigs with severe clinical disease in Hunan province of China, and also identified in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV). To further investigate the epidemic profile and genetic characteristics of the two viruses, 150 clinical samples were collected from 9 swine farms in Shaanxi and Henan provinces of China, and a SYBR Green I-based duplex quantitative real-time polymerase chain reaction (qPCR) was developed for detecting PCV4 and PRRSV simultaneously. The results showed the limits of detection were 41.1 copies/µL and 81.5 copies/µL for PCV4 and PRRSV, respectively. The detection rates of PCV4 and PRRSV were 8.00% (12/150) and 12.00% (18/150) respectively, and a case of co-infection with PCV4 and PRRSV was found in the lung tissue of a suckling pig with respiratory symptom. Subsequently, the complete genomic sequences of five PCV4 strains were obtained, of which one PCV4 strain (SX-ZX) was from Shaanxi province, and these strains were 1770 nucleotides in length and had 97.7%-99.4% genomic identity with 59 PCV4 reference strains. The genome characteristic of the SX-ZX strain was evaluated from three aspects, a "stem-loop" structure, ORF1 and ORF2. As essential elements for the replication, the 17-bp iterative sequence was predicted as the stem structure, in which three non-tandem hexamers were found at downstream with H1/H2 (12-CGGCACACTTCGGCAC-27) as the minimal binding site. Three of the five PCV4 strains were clustered into PCV4b, which was composed of Suidae, fox, dairy cow, dog and raccoon dog. Phylogenetic analysis revealed that seven PRRSV strains from the present study were clustered into the PRRSV-2 genotype. Collectively, these data extend our understanding of the genome characteristic of PCV4 as well as the molecular epidemiology and the genetic profile of PCV4 and PRRSV.

Research methods and efficacy of acupuncture in the treatment of Parkinson's disease: a scoping review of systematic reviews and meta-analyses.

Introduction: Research on acupuncture for Parkinson's Disease is growing rapidly. A scoping review examines emerging evidence and is important to guide policy and practice. The purpose of this scoping review was to examine the breadth and methodological quality of systematic reviews and meta-analyses, and to map the quality of evidence of these studies to evaluate the efficacy of acupuncture for treatment of PD. Methods: Seven literature databases were searched. Two researchers independently screened the literature and extracted relevant information (such as general characteristics, inclusion criteria, study results, and report quality).The inclusion criteria include publicly published systematic reviews/meta-analyses/systematic reviews of acupuncture treatment for Parkinson's disease. The research subjects are any patients who meet the diagnostic criteria for Parkinson's disease, and intervention measures include acupuncture treatment including electro acupuncture, scalp acupuncture, or combination with other treatment methods. The outcome indicators are all types of results related to PD and the effective measurement tools used. Results: A total of 23 systematic reviews and/or meta-analyses of studies were included. Most of the articles were published between 2019 and 2023 (47.8%). A total of 14 articles (60.9%) were evaluated and classified, and 89 (36.8.1%) of the 242 included articles were of medium and high quality. Discussion: This study comprehensively evaluates the quality and research methods of incorporating SRs/MAs, and concludes that acupuncture treatment for Parkinson's disease may be significant. Considering the shortcomings in research design and methodology, it is not possible to draw conclusions on the evidence of acupuncture treatment for PD at this stage, but it does not mean that acupuncture treatment is ineffective. We hope to focus on improving research design and methods in the study of acupuncture treatment for Parkinson's disease, an increase the credibility of research results.

Simultaneous determination of phenols in the four main original plants of the famous traditional Chinese medicine Shihu by pressurized capillary electrochromatography.

A rapid pressurized capillary electrochromatography (pCEC) method has been established for the simultaneous analysis of 11 phenols in the four main original plants of the famous traditional Chinese medicine (TCM) Shihu. The effects of wavelength, mobile phase, flow rate, pH value, concentration of buffer, and applied voltage were systematically studied. The investigated 11 phenols could be isolated in 35 min on a reversed-phase EP-100-20/45-3-C18 capillary column using the established method. To apply the established pCEC method, all phenols except tristin (11) were detected in the four Dendrobium plants. A total of 10 components were detected in D. huoshanense, 6 components in D. nobile, 3 components in D. chrysotoxum, and 4 components in D. fimbriatum. The consistent evaluation revealed that the similarities among the four original plants of Shihu were 38.2-86.0% based on the 11 polyphenols and 92.5-97.7% based on the pCEC fingerprints. These further suggested that the components of the four original plants of TCM Shihu might be significantly different. Further investigation should be conducted to confirm and evaluate if the four species could be used as the same medicine with the same amount according to Chinese Pharmacopoeia (ChP).