CCR5 and inflammatory storm.

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.

Virus-induced host genomic remodeling dysregulates gene expression, triggering tumorigenesis.

Virus-induced genomic remodeling and altered gene expression contribute significantly to cancer development. Some oncogenic viruses such as Human papillomavirus (HPV) specifically trigger certain cancers by integrating into the host's DNA, disrupting gene regulation linked to cell growth and migration. The effect can be through direct integration of viral genomes into the host genome or through indirect modulation of host cell pathways/proteins by viral proteins. Viral proteins also disrupt key cellular processes like apoptosis and DNA repair by interacting with host molecules, affecting signaling pathways. These disruptions lead to mutation accumulation and tumorigenesis. This review focuses on recent studies exploring virus-mediated genomic structure, altered gene expression, and epigenetic modifications in tumorigenesis.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Cotton BLH1 and KNOX6 antagonistically modulate fiber elongation via regulation of linolenic acid biosynthesis.

BEL1-LIKE HOMEODOMAIN (BLH) proteins are known to function in various plant developmental processes. However, the role of BLHs in regulating plant cell elongation is still unknown. Here, we identify a BLH gene, GhBLH1, that positively regulates fiber cell elongation. Combined transcriptomic and biochemical analyses reveal that GhBLH1 enhances linolenic acid accumulation to promote cotton fiber cell elongation by activating the transcription of GhFAD7A-1 via binding of the POX domain of GhBLH1 to the TGGA cis-element in the GhFAD7A-1 promoter. Knockout of GhFAD7A-1 in cotton significantly reduces fiber length, whereas overexpression of GhFAD7A-1 results in longer fibers. The K2 domain of GhKNOX6 directly interacts with the POX domain of GhBLH1 to form a functional heterodimer, which interferes with the transcriptional activation of GhFAD7A-1 via the POX domain of GhBLH1. Overexpression of GhKNOX6 leads to a significant reduction in cotton fiber length, whereas knockout of GhKNOX6 results in longer cotton fibers. An examination of the hybrid progeny of GhBLH1 and GhKNOX6 transgenic cotton lines provides evidence that GhKNOX6 negatively regulates GhBLH1-mediated cotton fiber elongation. Our results show that the interplay between GhBLH1 and GhKNOX6 modulates regulation of linolenic acid synthesis and thus contributes to plant cell elongation.

Effect of Intermittent Thoracic Paravertebral Block on Postoperative Nausea and Vomiting Following Thoracoscopic Radical Resection of the Lung Cancer: A Prospective Randomized Trial.

Purpose: To explore the benefits of ultrasound-guided intermittent thoracic paravertebral block (TPVB) combined with intravenous analgesia (PCIA) in alleviating postoperative nausea and vomiting (PONV) during video-assisted thoracic surgery (VATS). Patients and Methods: 120 patients with lung carcinoma undergoing VATS were included and divided into three groups: group S (single TPVB+PCIA), group I (intermittent TPVB+PCIA), and group P (PCIA). The patients' NRS scores, postoperative hydromorphone hydrochloride consumption, and intramuscular injection of bucinnazine hydrochloride were recorded. The incidence of PONV and complications were documented. Results: Compared with the group P, both group I and group S had significantly lower static NRS scores from 1-48 hours after the operation (P <0.05), and the dynamic NRS score of group I at the 1-48 hours after the operation were significantly decreased (P <0.05). Compared with the group P, the proportion of patients with PONV in group I was significantly lower (P <0.05), while there was no significant difference in group S. Moreover, the hospitalization period of patients in group I was significantly reduced compared with the other two groups (P <0.01), and the patient satisfaction was significantly increased compared with the group P (P <0.05). Conclusion: Intermittent TPVB combined with PCIA can reduce the postoperative pain and the occurrence of PONV.

Gibberellic acid promotes single-celled fiber elongation through the activation of two signaling cascades in cotton.

The agricultural green revolution spectacularly enhanced crop yield through modification of gibberellin (GA) signaling. However, in cotton, the GA signaling cascades remain elusive, limiting our potential to cultivate new cotton varieties and improve yield and quality. Here, we identified that GA prominently stimulated fiber elongation through the degradation of DELLA protein GhSLR1, thereby disabling GhSLR1's physical interaction with two transcription factors, GhZFP8 and GhBLH1. Subsequently, the resultant free GhBLH1 binds to GhKCS12 promoter and activates its expression to enhance VLCFAs biosynthesis. With a similar mechanism, the free GhZFP8 binds to GhSDCP1 promoter and activates its expression. As a result, GhSDCP1 upregulates the expression of GhPIF3 gene associated with plant cell elongation. Ultimately, the two parallel signaling cascades synergistically promote cotton fiber elongation. Our findings outline the mechanistic framework that translates the GA signal into fiber cell elongation, thereby offering a roadmap to improve cotton fiber quality and yield.

The safety of preoperative carbohydrate drinks in extremely elderly patients assessed by gastric ultrasonography: a randomized controlled trial.

BACKGROUND: Modern perioperative guidelines encourage drinking oral carbohydrates 2 h before management. Nevertheless, research on the safety of preoperative carbohydrate drinks, particularly in extremely elderly patients is lacking. We aimed to evaluate the safety of carbohydrate drinks 2 h before surgery in extremely elderly patients (≥ 80 years) using gastric ultrasonography. METHODS: We conducted a randomized prospective comparative study of 70 patients aged over 80 years who were scheduled for total knee arthroplasty, hip fracture or humerus fracture surgery. These patients were randomly assigned to the carbohydrate group (n = 35), which fasted from midnight, except for drinking 355 mL of a carbohydrate-containing fluid 2 h before surgery, or the fasting group (n = 35), which fasted from midnight and drank no fluid before surgery. The primary outcome of the study was the cross-sectional area (CSA) of the gastric antrum in the right lateral decubitus position (RLDP) before surgery. The secondary outcomes included CSA in the supine position, intraoperative blood glucose levels and their variability coefficients, Perlas grade, and the visual analog scale of subjective feelings. RESULTS: The CSA in the RLDP and supine positions revealed no differences between the carbohydrate and fasting groups at 0 h preoperatively (P > 0.05). In the qualitative assessment, preoperative 0-h Perlas grading did not differ significantly between the groups (P > 0.05). From 2 h before surgery to transfer out of the post-anesthesia care unit, the average blood glucose level of patients in the carbohydrate group was significantly higher than that in the fasting group (P < 0.001) but remained within the normal range. Moreover, the blood glucose variability coefficient was significantly lower in the carbohydrate group than in the fasting group (P = 0.009). Oral intake of 355 mL carbohydrates before surgery significantly relieved patients' feelings (P < 0.001). CONCLUSION: Preoperative consumption of carbohydrate drinks 2 h before surgery is safe in "healthy" extremely elderly patients. In addition, preoperative drinking has potential value in maintaining ideal blood glucose levels and stable blood glucose fluctuations perioperatively and improving subjective perceptions of preoperative preparation. This finding warrants further investigation in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number ChiCTR1900024812), first registered on 29/07/2019.

Clinical Characteristics and Molecular Genetic Analysis of a Pedigree with Glanzmann's Thrombasthenia.

Objective: The objective of this study was to investigate the clinical phenotype and genetic etiology of Glanzmann's thrombasthenia in a consanguineous pedigree. Methods: Clinical data and ancillary test results were collected from pedigrees with Glanzmann's thrombasthenia. High-throughput sequencing was used to detect variants in the proband. Candidate variants were verified by Sanger sequencing. Results: Two patients in the pedigree were homozygous for the c.2248C>T (p. Arg750Ter) variant of the ITGB3 gene. The parents and maternal grandmother, who didn't have any recurrent haemorrhage, were found to carry a heterozygous c.2248C>T variant of the ITGB3 gene, which was absent in the aunt and paternal grandmother. Conclusion: The homozygous variant c.2248C>T (p. Arg750Ter) in the ITGB3 gene underlies the disease in this pedigree. This diagnosis will facilitate genetic counselling in this pedigree for better patient management and life guidance.

High-Efficiency Ultraviolet Electroluminescence from Multi-Resonance Phosphine Oxide Polycyclic Aromatics.

Efficient ultraviolet (UV) electroluminescent materials remain a great challenge, since short peak wavelength <400 nm and narrow full width at half maximum (FWHM) <50 nm are simultaneously required. In this sense, multi-resonance (MR) thermally activated delayed fluorescence (TADF) emitters featuring narrow-band emissions hold the promise for UV applications. Herein, a novel MR-TADF skeleton featuring carbazole-phosphine oxide (P=O) fused aromatics is developed to construct the first two UV MR emitters named CzP2PO and tBCzP2PO. In addition to synergistic resonance effects of P=O and N atom, sp3 -hybrid P atom renders the curved polycyclic planes of CzP2PO and tBCzP2PO, giving rise to their narrowband UV emissions with peak wavelengths <390 nm and FWHM<35 nm. Besides configuration quasi-planarization for radiation enhancement and quenching suppression, P=O moiety further enhances singlet-triplet coupling to facilitate reverse intersystem crossing, resulting in the state-of-the-art photoluminescence quantum yield of 62 % in tBCzP2PO doped films. As consequence, tBCzP2PO endowed its UV organic light-emitting diodes with the peak at 382 nm and FWHM of 32 nm, and especially the record-high external quantum efficiency (EQE) of 15.1 % among all kinds of UV devices. Our results demonstrate great potential of P=O based MR emitters in practical applications including optoelectronics, biology and medicine science.

Fabrication and characterization of curcumin-loaded nanoparticles using licorice protein isolate from Radix Glycyrrhizae.

Licorice was widely used in food and herbal medicine. In its extract industry, a substantial amount of licorice protein was produced and discarded as waste. Herein, we extracted Licorice Protein Isolate (LPI) and explored its potential as a curcumin nanocarrier. Using a pH-driven method, we fabricated LPI-curcumin nanoparticles with diameters ranging from 129.30 ± 3.21 nm to 75.03 ± 1.19 nm, depending on the LPI/curcumin molar ratio. The formation of LPI-curcumin nanoparticles was primarily driven by hydrophobic interactions, with curcumin entrapped in LPI being in an amorphous form. These nanoparticles significantly enhanced curcumin properties in terms of solubility, photochemical stability, and stability under varying pH, storage, and physiological conditions. Moreover, the loaded curcumin exhibited a 2.58-fold increase in cellular antioxidant activity on RAW 264.7 cells and a 1.86-fold increase in antitumor activity against HepG2 cells compared to its free form. These findings suggested that LPI could potentially serve as a promising novel delivery material.

Higenamine exerts antidepressant effect by improving the astrocytic gap junctions and inflammatory response.

BACKGROUND: Depression is a refractory psychiatric disorder closely associated with dysfunction of the gap junctions (GJs) between astrocytes as well as neuroinflammation. Higenamine (Hig) is a potent cardiotonic ingredient in Fuzi (i.e., Aconitum carmichaeli Debx.) with anti-inflammatory and antioxidant effects, which has a significant protective effect on damaged nerve cells and has great potential for the treatment of neuropsychiatric diseases. METHODS: Rats were stimulated by chronic unpredictable stress (CUS) for 28 days while given Hig (5, 10, 20 mg/kg) and then analyzed behaviorally by the open field test, sucrose preference test, and forced swimming test. Changes in astrocyte GJs function and morphology were observed by dye transfer and transmission electron microscopy, respectively. Expression and phosphorylation of connexin 43 (Cx43) were analyzed by Western blot. Also, considering the close relationship between depression and neuroinflammation, we determined the inflammatory response in serum with ELISA kits and analyzed the expression of inflammation-related proteins with Western blot. RESULTS: Hig ameliorated CUS-induced depression-like behavior in rats. Hig administration improved gap junctional dysfunction in astrocytes, reduced gap junctional gaps and elevated the expression of Cx43 and decreased the phosphorylation of Cx43. Meanwhile, Hig administration was also able to attenuate the inflammatory response that occurs after CUS in rats. LIMITATIONS: For the role of Cx43 in depression, we did not validate it more deeply in animal models with knockout Cx43. In addition, GJs dysfunction might be associated with the inflammatory response seen in depression, but this needs to be further investigated. CONCLUSIONS: Hig ameliorates depression and exerts its antidepressant effect possibly by improving the dysfunctional GJs between astrocytes and the inflammatory response.

A novel pathogenic splicing mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa verified by minigene splicing assay.

AIM: To report a novel splicing mutation in the RPGR gene (encoding retinitis pigmentosa GTPase regulator) in a three-generation Chinese family with X-linked retinitis pigmentosa (XLRP). METHODS: Comprehensive ophthalmic examinations including best corrected visual acuity, fundus photography, vision field, and pattern-visual evoked potential were performed to identify the disease phenotype of a six-year-old boy from the family (proband). Genomic DNA was extracted from peripheral blood of five available members of the pedigree. Whole-exome sequencing (WES), Sanger sequencing, and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR. Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants. RESULTS: The proband was diagnosed as having retinitis pigmentosa (RP). He had severe symptoms with early onset. A novel splicing mutation, c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing. Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped, leading to the subsequent deletion of 623 correct amino acids (c.529_619del p.Val177Glnfs*16). CONCLUSION: We identify a novel splice donor site mutation causing aberrant splicing of RPGR. Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.

Novel antidepressant mechanism of hypericin: Role of connexin 43-based gap junctions.

Hypericin is widely utilized for its precise antidepressant properties, but its exact antidepressant mechanism remains unclear. Gap junctions, which were predominantly expressed in astrocytes in the central nervous system, are concerned with the pathogenesis of depression. However, the role of hypericin in gap junctional dysfunction in depression has rarely been investigated. Here, we found that gap junctions were ultra-structurally broadened in the chronic unpredictable stress (CUS) rat model of depression, while hypericin repaired the dysfunction of gap junctions. Suppression of gap junctions by bilateral injection of carbenoxolone (CBX) in the prefrontal cortex of rats significantly inhibited the restoration of gap junctional dysfunction in depression by hypericin. Meanwhile, hypericin failed to show antidepressant benefits. Furthermore, in corticosterone (CORT)-stimulated primary astrocytes derived from neonatal rats, hypericin dramatically reversed the phosphorylation of connexin 43 (Cx43), normalizing the expression of Cx43 and thereby ameliorating gap junctional dysfunction. Comparatively, CBX inhibited the remission of hypericin on gap junctional intercellular communication function. Gap junctional function might be a novel therapeutic target for hypericin in the treatment of depression and provide potential novel insights into the antidepressant mechanism of other herbal ingredients.

Incidental nanoparticles in black tea alleviate DSS-induced ulcerative colitis in BALB/c mice.

As the dominant herbal drink consumed worldwide, black tea exhibits various health promoting benefits including amelioration of inflammatory bowel diseases. Despite extensive studies on the tea's components, little is known about the bioactivities of nanoparticles (NPs) which were incidentally assembled in the tea infusion and represent the major components. This study investigated the alleviative effects of black tea infusion, the isolated black tea NPs, and a mixture of caffeine, epigallocatechin-3-gallate, gallic acid and epicatechin gallate on dextran sodium sulfate (DSS)-induced ulcerative colitis. The results showed that both the black tea infusion and the NPs significantly alleviated colitis, suppressed the mRNA levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, and suppressed the DSS-induced loss of cell-cell junction proteins (e.g., E-cadherin, ZO-1, and claudin-1) and increase of p-STAT3. The mixture of four tea components, which is the analogue of bioactive payloads carried by the NPs, was much less effective than the tea infusion and NPs. It shows that the NPs elevate the efficiency of polyphenols and caffeine in black tea in restoring the intercellular connection in the intestine, inhibiting mucosal inflammation, and alleviating ulcerative colitis. This work may inspire the development of tea-based therapeutics for treating inflammatory bowel diseases and have wide influences on value-added processing, quality evaluation, functionalization, and innovation of tea and other plant-based beverages.

Boosting mineralized organic pollutants by using a sulfur-vacancy CdS photocatalyst.

Photocatalytic mineralization of organic pollutions and simultaneously converting CO2 to CO (tetracycline → CO2 → CO) represents a fascinating way to solve the environmental and energy crisis. This work demonstrates the excellent mineralization and CO2 reduction performance of S-vacancy CdS and reveals the high efficiency of the carbon self-recycling two-in-one photocatalytic system.

Serum Proteomic Signatures in Umbilical Cord Blood of Preterm Neonates Delivered by Women with Gestational Diabetes.

Background: Women who develop diabetes during pregnancy are at higher risk of preterm birth. Here, we identified differentially expressed proteins (DEPs) in the serum of umbilical cord blood samples obtained from preterm neonates delivered by women with gestational diabetes to provide therapeutic targets for clinical drug development. Materials and Methods: Umbilical cord blood was collected after delivery of preterm neonates by women with gestational diabetes and after delivery of healthy neonates by women without diabetes. DEPs in the serum samples were identified using liquid chromatography-tandem mass spectrometry. Gene Ontology (GO), cluster analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions associated with these DEPs. Enzyme linked immunosorbent assay was used to confirm the key DEPs. Results: We found that 21 proteins were significantly upregulated, and 51 proteins were significantly downregulated in 72 DEPs in serum samples. GO analyses showed that the DEPs were mainly associated with the GO terms cellular process, biological regulation, cellular anatomical entity, and binding. KEGG signaling pathway analysis indicated that most of the upregulated DEPs were associated with the complement and coagulation cascades, Staphylococcus aureus infection, pertussis, HIF-1 signaling pathway and PPAR signaling pathway and that most of the downregulated DEPs were associated with the complement and coagulation cascades, dilated cardiomyopathy, pathways in cancer, Chagas disease, and hypertrophic cardiomyopathy. The results of KEGG pathway annotation and enrichment analyses indicated that changes in the complement and coagulation cascades may be importantly associated with preterm delivery of neonates by women with gestational diabetes. The key DEPs were confirmed by enzyme linked immunosorbent assay. Conclusion: Our proteomics and bioinformatics analyses identified several key proteins and the complement and coagulation cascades pathway that warrant further investigation as potential novel therapeutic targets in preterm delivery among women with gestational diabetes.

Neurotrophic basis to the pathogenesis of depression and phytotherapy.

Depression is a major neuropsychiatric disease that considerably impacts individuals' psychosocial function and life quality. Neurotrophic factors are now connected to the pathogenesis of depression, while the definitive neurotrophic basis remains elusive. Besides, phytotherapy is alternative to conventional antidepressants that may minimize undesirable adverse reactions. Thus, further research into the interaction between neurotrophic factors and depression and phytochemicals that repair neurotrophic factors deficit is highly required. This review highlighted the implication of neurotrophic factors in depression, with a focus on the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), and detailed the antidepressant activities of various phytochemicals targeting neurotrophic factors. Additionally, we presented future opportunities for novel diagnostic and therapeutic strategies for depression and provided solutions to challenges in this area to accelerate the clinical translation of neurotrophic factors for the treatment of depression.

A bibliometric analysis of chronic obstructive pulmonary disease and COVID-19.

The coronavirus disease 2019 (COVID-19) outbreak became the worst epidemic in decades. Since its inception, COVID-19 has had a dramatic impact on chronic obstructive pulmonary disease (COPD) patients. This study explores explore the current status, hot spots, and research frontiers of COVID-19 and COPD based on a bibliometric approach. The Web of Science Core Collection was used to search the literature related to COPD and COVID-19, and VOSviewer and CiteSpace software were applied to analyze the distribution characteristics, research hotspots, and research frontiers of literature in related fields and to map the scientific knowledge domains. A total of 816 valid publications were included, among which USA, China, and England are the core countries/regions publishing related literature, and the research institutions are concentrated in Huazhong University of Science and Technology (18 papers), University College London (17 papers), and Imperial College London (16 papers). Guan WJ is the most prolific author with the most articles. The journals with the most publications are PLOS ONE, JOURNAL OF CLINICAL MEDICINE, and FRONTIERS IN MEDICINE. The main research hotspots in this field are clinical features, disease management, and mechanism research. By constructing COPD and COVID-19 research network diagrams, we reveal the hot spots, frontiers, and development trends of relevant research fields, which provide a reference for subsequent researchers to quickly grasp the current status of related research fields.

A conserved brassinosteroid-mediated BES1-CERP-EXPA3 signaling cascade controls plant cell elongation.

Continuous plant growth is achieved by cell division and cell elongation. Brassinosteroids control cell elongation and differentiation throughout plant life. However, signaling cascades underlying BR-mediated cell elongation are unknown. In this study, we introduce cotton fiber, one of the most representative single-celled tissues, to decipher cell-specific BR signaling. We find that gain of function of GhBES1, a key transcriptional activator in BR signaling, enhances fiber elongation. The chromatin immunoprecipitation sequencing analysis identifies a cell-elongation-related protein, GhCERP, whose transcription is directly activated by GhBES1. GhCERP, a downstream target of GhBES1, transmits the GhBES1-mediated BR signaling to its target gene, GhEXPA3-1. Ultimately, GhEXPA3-1 promotes fiber cell elongation. In addition, inter-species functional analysis of the BR-mediated BES1-CERP-EXPA3 signaling cascade also promotes Arabidopsis root and hypocotyl growth. We propose that the BES1-CERP-EXPA3 module may be a broad-spectrum pathway that is universally exploited by diverse plant species to regulate BR-promoted cell elongation.