Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.

Cellular death in the body can occur through different processes,including apoptosis,pyroptosis and necrotic apoptosis,etc.PANoptosis is a newly discovered form of inflammatory cell death in recent years.It can be triggered by various stimulating factors and integrates multiple components that can induce cell death to assemble into various types of macromolecular complexes-PANoptosome,which then mediates cell death.Given the impact of PANoptosis on the entire disease spectrum,promoting or inhibiting its occurrence process may prevent the development of various diseases.The review summarizes the research progress on the occurrence mechanism of PANoptosis and its role in some diseases,and explores the crosstalk among multiple programmed cell death pathways,aiming to provide new ideas for the treatment of related diseases.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.
Humans ; Moxibustion ; Acupuncture Therapy/methods* ; Acupuncture ; Clinical Protocols ; Migraine Disorders/therapy*

Objective: To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role. Methods: Forty-eight apolipoprotein E^-/- mice fed a high fat diet were used to construct the atherosclerosis model. They were randomly divided into 4 groups with 12 rats in each group. They were treated with rosuvastatin, vascular endothelial growth factor-C (VEGF-C) and rosuvastatin+VEGF-C inhibitors as experimental group, and no intervention measures were given in control group. After 8 weeks, aortic plaque area, high density lipoprotein cholesterol (HDL-C) content in lymph fluid, the function of popliteal lymphatic drainage of peripheral Evans blue, and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein (HDL) were detected. Subsequently, the effects of rosuvastatin on proliferation, migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1 (SR-B1) on lymphoendothelial cells at different concentrations were detected. Results: Compared with the control group, Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque (P<0.05). In addition to rosuvastatin plus VEGF-C inhibitor, the intra-aortic plaque area increased (P<0.05). Compared with the control group, Rosuvastatin could increase the content of HDL-C in lymphatic fluid (P<0.05), enhance the drainage function of lymphatic vessels, and enhance the capacity of HDL in the transport tissue fluid of lymphatic system. Compared with the control group, VEGF-C increased the content of HDL-C in mouse lymph fluid (P<0.01), enhanced the drainage function of popliteal lymphatic canal, and enhanced the ability of lymphatic system to transport HDL. With the addition of VEGF-C inhibitor on the basis of rosuvastatin, the content of HDL-C in lymph fluid was reduced, the drainage of popliteal lymphatic canal was interrupted, and the ability of lymphatic system to transport HDL was reduced. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.
Rats ; Mice ; Animals ; Rosuvastatin Calcium/therapeutic use* ; Vascular Endothelial Growth Factor C ; Endothelial Cells/metabolism* ; Atherosclerosis/drug therapy* ; Plaque, Atherosclerotic ; Cholesterol, HDL ; Lymphatic System/metabolism*

OBJECTIVE: To analyze the association between outdoor artificial light-at-night (ALAN) exposure and overweight and obesity among children and adolescents aged 9 to 18 years in China. METHODS: Using follow-up data of 5 540 children and adolescents aged 9 to 18 years conducted from November 2019 to November 2020 in eight provinces of China, latitude and longitude were determined based on school addresses, and the mean monthly average nighttime irradiance at the location of 116 schools was extracted by the nearest neighbor method to obtain the mean outdoor ALAN exposure [unit: nW/(cm²·sr)] for each school. Four indicators of overweight and obesity outcomes were included: Baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. Mixed effects Logistic regression was used to explore the association between ALAN exposure levels (divided into quintiles Q1-Q5) and baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. In addition, a natural cubic spline function was used to explore the exposure response association between ALAN exposure (a continuous variable) and the outcomes. RESULTS: The prevalence of baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence among the children and adolescents in this study were 21.6%, 16.3%, 2.9% and 12.8%, respectively. The OR value for the association between ALAN exposure and baseline overweight and obesity was statistically significant when ALAN exposure levels reached Q4 or Q5, 1.90 (95%CI: 1.26-2.86) and 1.77 (95%CI: 1.11-2.83), respectively, compared with the children and adolescents in the Q1 group of ALAN exposure. Similar to the results for baseline overweight and obesity, the OR values for the association with persistent overweight and obesity were 1.89 (95%CI: 1.20-2.99) and 1.82 (95%CI: 1.08-3.06) when ALAN exposure levels reached Q4 or Q5, respectively, but none of the OR values for the association between ALAN and overweight and obesity progression and overweight and obesity incidence were statistically significant. Fitting a natural cubic spline function showed a non-linear trend between ALAN exposure and persistent overweight and obesity. CONCLUSION There is a positive association between ALAN exposure and overweight and obesity in children and adolescents, and the promotion of overweight obesity in children and adolescents by ALAN tends to have a cumulative effect rather than an immediate effect. In the future, while focusing on the common risk factors for overweight and obesity in children and adolescents, there is a need to improve the overweight and obesity-causing nighttime light exposure environment.
Humans ; Adolescent ; Child ; Overweight/etiology* ; Pediatric Obesity/etiology* ; Light Pollution ; Risk Factors ; China/epidemiology*