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

Human cytomegalovirus (HCMV) poses a significant risk of neural damage during pregnancy. As the most prevalent intrauterine infectious agent in low- and middle-income countries, HCMV disrupts the development of neural stem cells, leading to fetal malformations and abnormal structural and physiological functions in the fetal brain. This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
Humans ; Cytomegalovirus Infections/virology* ; Wnt Signaling Pathway ; Pregnancy ; Female ; Cytomegalovirus/physiology* ; Pregnancy Complications, Infectious/virology* ; Congenital Abnormalities/virology* ; Animals

Shewanella oneidensis MR-1, a Gram-negative bacterium with a significant role in the adsorption and reduction of uranium in wastewater and a quorum-sensing effect, can be used to remove uranium from wastewater. Exogenous signaling molecules (acyl-homoserine lactones, AHLs) can be added to induce the quorum sensing behavior for rapid biofilm formation, thereby improving the removal efficiency of this bacterium for uranium. Extracellular polymeric substances (EPS), as the significant components of biofilm, play a key role in biofilm formation. To investigate the quorum sensing behavior induced by AHLs, we systematically investigated the effects of AHLs on the EPS secretion and biofilm properties of S. oneidensis MR-1 by regulating parameters such as AHL species, concentration, addition time point, and contact time. The results showed that the addition of 10 μmol/L N-butyryl-l-homoserine lactone (C4-HSL) after 6 h of culture and continued incubation to reach the time point of 72 h significantly promoted the secretion of EPSs, in which the content of extracellular proteins and extracellular polysaccharides was increased by 15.2% and 28.2%, respectively, compared with that of the control group. The biofilm electrodes induced by signaling molecules showed superior properties, which were evidenced by an increase of exceeding 20 μm in biofilm thickness, an increase of 33.9% in the proportion of living cells, enhanced electroactivity, and an increase of 10.7% in the uranium removal rate. The biofilm electrode was confirmed to immobilize uranium in wastewater mainly by electrosorption, physicochemical adsorption, and electro-reduction through characterization means such as X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). This study provides a new technical idea for the efficient recovery of uranium in wastewater and enriches the theoretical system of quorum sensing regulation of electroactive biofilms.
Biofilms/drug effects* ; Acyl-Butyrolactones/pharmacology* ; Quorum Sensing/drug effects* ; Uranium/metabolism* ; Shewanella/metabolism* ; Adsorption ; Uranium Compounds/metabolism* ; Wastewater/chemistry* ; Biodegradation, Environmental ; Extracellular Polymeric Substance Matrix/metabolism*

BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Retrospective Studies ; Translocation, Genetic ; Chromosome Aberrations ; Karyotyping

Soybean mosaic virus (SMV) is a critical pathogen that reduces the soybean yield and seed quality worldwide, and SMV has a restricted natural host range. In this study, we used sequence-independent amplification (SIA) methods to identify the viruses that may cause the Atractylodes macrocephala Koidz disease. Results revealed that there is SMV in diseased Atractylodes macrocephala leaves, and we named this isolate as SMV-Am. To further characterize the genomic structural and phylogenetic relationships of SMV-Am, genomic dsRNA was extracted, and the genomic sequence was amplified by RT-PCR and RACE. The results of bioinformatics analysis showed that the genomic RNA of SMV-Am is 9587 nucleotides in length, which conforms to the typical characteristics of Potyvirus. According to the sequence alignment of complete nucleotide sequences, SMV-Am showed the highest level of nucleotide homology and amino acid sequences to SMV-Liaoning, 96. 57% and 98. 86%, respectively. In addition, phylogenetic analysis based on the nucleotide sequences of other SMV isolates of SMV-Am revealed that SMV-Am was most closely related to SMV-Liaoning. Then, the SMV-Am protein was further analyzed by I-TASSER and PyMOL software, revealing that the key amino acid mutations led to the structural changes of P1, HC-Pro, P3, 6K2, NIa-pro and NIb proteins, with P1 the most obvious. Finally, recombination has been detected at the position of 6560-8950 nucleotides, the main parent is the isolate SMV-XFQ012 (accession number KP710875. 1), and the secondary parent is isolate SMV-pCB301-SC15 (accession number MH919386. 1). This study is the first report of SMV in Atractylodes macrocephala Koidz, and these results are expected to provide a scientific basis for the prevention and control of SMV infection on Atractylodes macrocephala Koidz.

OBJECTIVE: Vitamin D and Toll-like receptor-4 (TLR-4) inhibition are involved in the protection of keratinocytes. The effects of combination of 1,25(OH) ₂D ₃ and TLR-4 inhibitor on the protection of keratinocytes against ultraviolet radiation B (UVB) irradiation remain unclear. This study was undertaken to explore the effects of combination of 1,25(OH) ₂D ₃ and TAK-242 (TLR-4 inhibitor) on the damage to HaCaT cells caused by UVB irradiation. METHODS: In vitro, HaCaT cells were treated with 1,25(OH) ₂D ₃ or/and TAK-242 prior to UVB irradiation at the intensity of 20 mJ/cm ², then the production of reactive oxygen species (ROS), cell migration, apoptosis of cells, and the expression of oxidative stress, endoplasmic reticulum stress, and apoptosis related proteins were determined. RESULTS: Compared with the HaCaT cells treated with 1,25(OH) ₂D ₃ or TAK-242, the cells treated with both 1,25(OH) ₂D ₃ and TAK-242 showed, 1) significantly lower production of ROS ( P < 0.05); 2) significantly less apoptosis of HaCaT cells ( P < 0.05); 3) significantly lower expression of NF- κB, Caspase-8, Cyto-C, Caspase-3 ( P < 0.05). CONCLUSION The combination of 1,25(OH) ₂D ₃ and TAK-242 could produce a better protection for HaCaT cells via inhibiting the oxidative stress, endoplasmic reticulum stress and apoptosis than 1,25(OH) ₂D ₃ or TAK-242 alone.
Humans ; HaCaT Cells ; NF-kappa B ; Reactive Oxygen Species ; Toll-Like Receptor 4 ; Ultraviolet Rays/adverse effects* ; Cholecalciferol/analogs & derivatives*

Zucchini yellow mosaic virus (ZYMV) is a destructive cucurbit virus that causes extensive losses in the yield and quality of cucurbits (e.g., zucchini). At present, the analysis of genetic evolution of ZYMV is mainly based on CP sequence, and there has been little progress in addressing its phylogenetic relationships and evolution at the whole genome level. In this study, the whole genome sequences of ZYMV isolated from Shanxi Wenshui (ZYMV-WS) and 109 other reported ZYMV isolates were used to explore their phylogenetic relationships. The results showed that ZYMV-WS had the highest level of nucleotide homology (94.35%) to ZYMV-SXSG, and the amino acid sequences of ZYMV-BR3 were identical (97.37%) to those of ZYMV-WS. In addition, the phylogenetic analysis of ZYMV revealed that all the isolates were clustered into two major branches, and its population structure assessment demonstrated a marked genetic differentiation between A4 and B. Furthermore, we also discovered the sites of specific amino-acid alteration, and their possible association with functional changes. These results will help to better understand the genetic diversity and phylogenetic process of ZYMV, and lay a theoretical foundation for the effective prevention and control of ZYMV infection in the near future.

Krüppel-like factor 7 (KLF7) is a negative regulator of adipogenesis, whereas hypoxia-inducible factor 1 (HIF1) promotes anoxic-induced adipose tissue development in mammals. Our previous ChIP-seq analysis showed that one of the KLF7 binding peaks was present upstream of hypoxia-inducible factor 1 alpha (HIF1α), indicating that KLF7 may regulate HIF1α transcription. For this purpose, ChIP-PCR was used to verify ChIP-seq results, which showed that KLF7 directly bound to the HIF1α upstream region. Dual luciferase reporter and qRT-PCR results showed that KLF7 overexpression significantly decreased the luciferase reporter activity of HIF1α (- 4 432/- 4 182) (P < 0. 01) and inhibited HIF1α expression. After the deletion of KLF7 binding motif “TGCGCAGCAA” (- 4 300/-4 290) predicted by bioinformatics, the luciferase reporter activity of HIF1α (-4 432/-4 182) was significantly enhanced compared with wild-type plasmid (P<0. 01). Furthermore, Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) at the age of 1-7 weeks from the 19

OBJECTIVE: To compare the clinical effects of closed reduction and internal fixation with limited transtarsal sinus incision in the treatment of Sanders type II calcaneal fractures. METHODS: From June 2015 to February 2018, 60 patients with Sanders type II calcaneal fractures were treated by minimally invasive method. According to the different treatment methods, they were divided into two groups: closed prying reduction and internal fixation with hollow nails(group A) and limited transtarsal sinus incision internal fixation (group B). There were 34 cases in group A, including 22 males and 12 females, aged 21 to 60(38.90±3.25) years old, 14 cases of Sanders type IIA, 14 cases of Sanders type IIB and 6 cases of Sanders type IIC. There were 20 cases in group B, including 14 males and 6 females, aged 20 to 59(39.20±2.96) years old, 8 cases of Sanders type IIA, 9 cases of Sanders type IIB and 3 cases of Sanders type IIC. Calcaneal height, calcaneal width, Gissane angle and Bohler angle were measured before and after operation. The complications, hospitalization time and cost were compared. Functional evaluation was performed by AOFAS score system one year after operation. RESULTS: Fifty-four cases were followed up for 6 to 16(11.40±2.55) months and 6 cases were lost. All the wounds healed in grade A without complications such as skin infection and necrosis. There were 1 case of nerve injury in group A, 2 cases of tendon entrapment, 2 cases of nerve injury in group B, there was no significant difference(>0.05). There was no significant difference in calcaneal width, height, Bohlers angle and Gissane angle between group A and group B (>0.05). There was no significant difference in AOFAS score between group A and group B(89.2±4.7 vs 88.7±4.8, >0.05). The hospitalization expenditure and length of stay in group A were(5 021.25±1 047.19) yuan, (6.31±4.75) d, and those in group B were(13 591.35±1 975.21) yuan, (9.65±3.42) d, respectively, with significant difference(<0.05). CONCLUSIONS Closed reduction and internal fixation is as effective as transtarsal sinus incision reduction and internal fixation for Sanders typeIIfracture. It has the advantages of less trauma and fewer complications. Closed reduction and hollow nail fixation group can significantly shorten hospitalization time, reduce hospitalization costs, and is more economical. It is worth recommending, but attention should be paid to avoid choosing to comminute serious calcaneal fracture.
Adult ; Ankle Injuries ; Calcaneus ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult