Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

BACKGROUND: Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies. METHODS: The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted. RESULTS: In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China's CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging. CONCLUSIONS The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.
Humans ; Non-alcoholic Fatty Liver Disease/mortality* ; Global Burden of Disease ; China/epidemiology* ; Prevalence ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Middle Aged ; Chronic Disease ; Adult ; Quality-Adjusted Life Years ; Liver Diseases/epidemiology* ; Aged

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

The chemical constituents of the petroleum ether extract derived from the 90% ethanol extract of Elephantopus scaber were investigated. By silica gel column chromatography, C_(18), MCI column chromatography and semi-preparative high performance liquid chromatography, ten compounds were isolated. Their structures were identified as 3β-hydroxy-6β,7β-epoxytaraxeran-14-ene(1), 3β-hydroxyolean-12-en-28-oic acid(2), D-friedoolean-14-ene-3β,7α-diol(3), 3β-hydroxy-11α-methoxyolean-12-ene(4), 3β-hydroxyolean-11,13(18)-diene(5), 11α-hydroxy-β-amyrin(6), betulinic acid(7), 3β-hydroxy-30-norlupan-20-one(8), 6-acetonylchelerythrine(9), and 4',5'-dehydrodiodictyonema A(10) by analysis of the 1D NMR, 2D NMR, MS, and IR spectral data. Among them, compound 1 was a new triterpene and other compounds except compounds 2 and 7 were isolated from this plant for the first time.
Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Asteraceae/chemistry* ; Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female