Common alterations in parallel metabolomic profiling of serum and spinal cord and mechanistic studies on neuropathic pain following PPARα administration.

Neuropathic pain (NP) is usually treated with analgesics and symptomatic therapy with poor efficacy and numerous side effects, highlighting the urgent need for effective treatment strategies. Recent studies have reported an important role for peroxisome proliferator-activated receptor alpha (PPARα) in regulating metabolism as well as inflammatory responses. Through pain behavioral assessment, we found that activation of PPARα prevented chronic constriction injury (CCI)-induced mechanical allodynia and thermal hyperalgesia. In addition, PPARα ameliorated inflammatory cell infiltration at the injury site and decreased microglial activation, NOD-like receptor protein 3 (NLRP3) inflammasome production, and spinal dendritic spine density, as well as improved serum and spinal cord metabolic levels in mice. Administration of PPARα antagonists eliminates the analgesic effect of PPARα agonists. PPARα relieves NP by inhibiting neuroinflammation and functional synaptic plasticity as well as modulating metabolic mechanisms, suggesting that PPARα may be a potential molecular target for NP alleviation. However, the effects of PPARα on neuroinflammation and synaptic plasticity should be further explored.

Interior decorative volatile organic compounds exposure induces sleep disorders through aberrant branched chain amino acid transaminase 2 mediated glutamatergic signaling resulting from a neuroinflammatory cascade.

Air pollution has been recognized as a contributing factor to sleep disorders (SD), which have been correlated with an elevated susceptibility to a variety of human diseases. Nevertheless, research has not definitively established a connection between SD and interior decorative volatile organic compounds (ID-VOCs), a significant indoor air pollutant. In this study, we employed a mouse model exposed to ID-VOCs to explore the impacts of ID-VOCs exposure on sleep patterns and the potential underlying mechanism. Of the 23 key compositions of ID-VOCs identified, aromatic hydrocarbons were found to be the most prevalent. Exposure to ID-VOCs in mice resulted in SD, characterized by prolonged wake fullness and decreased sleep during the light period. ID-VOCs exposure triggered neuroinflammatory responses in the suprachiasmatic nucleus (SCN), with microglia activation leading to the overproduction of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and complement component 1q (C1q), ultimately inducing A1 astrocytes. Consequently, the upregulation of branched chain amino acid transaminase 2 (BCAT2) in A1 astrocytes resulted in elevated extracellular glutamate and disruption of the wake-sleep transition mechanism, which might be the toxicological mechanism of SD caused by ID-VOCs.

Variations in the Cadherin 23 Gene Associated With Noise-Induced Hearing Loss.

Background: The relationship between CDH23 gene variants and NIHL is unclear. This study investigates the association between cadherin 23 (CDH23) gene variants and noise-induced hearing loss (NIHL). Methods: This is a case-control study. Workers who were exposed to noise from a steel factory in North China were recruited and divided into two groups: the case group (both ears' high-frequency threshold average [BHFTA] ≥40dB) and the control group (BHFTA ≤25 dB). This study used the generalised multifactor dimensionality reduction method to analyse the association among 18 single-nucleotide polymorphisms (SNPs) in CDH23 and NIHL. Logistic regression was performed to investigate the main effects of SNPs and the interactions between cumulative noise exposure (CNE) and SNPs. Furthermore, CNE was adjusted for age, gender, smoking, drinking, physical exercise and hypertension. Results: This study recruited 1,117 participants. The results showed that for rs11592462, participants who carried the GG genotype showed an association with NIHL greater than that of those who carried the CC genotype. Accordingly, genetic variation in the CDH23 gene could play an essential role in determining individual susceptibility to NIHL. Conclusion: Genetic variations in the CDH23 gene may play an important role in determining individual susceptibility to NIHL. These results provide new insight into the pathogenesis and early prevention of NIHL.

Exploring Prenatal Exposure to Halogenated Compounds and Its Relationship with Birth Outcomes Using Nontarget Analysis.

Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks.

Combining fecal 16 S rRNA sequencing and spinal cord metabolomics analysis to explain the modulatory effect of PPARα on neuropathic pain.

BACKGROUND: Existing evidence suggests that the composition of the gut microbiota is associated with neuropathic pain (NP), but the mechanistic link is elusive. Peroxisome proliferator-activated receptor α (PPARα) has been shown to be a pharmacological target for the treatment of metabolic disorders, and its expression is also involved in inflammatory regulation. The aim of this study was to investigate the important modulatory effects of PPARα on gut microbiota and spinal cord metabolites in mice subjected to chronic constriction injury. METHODS: We analyzed fecal microbiota and spinal cord metabolic alterations in mice from the sham, CCI, GW7647 (PPARα agonist) and GW6471 (PPARα antagonist) groups by 16 S rRNA amplicon sequencing and untargeted metabolomics analysis. On this basis, the intestinal microbiota and metabolites that were significantly altered between treatment groups were analyzed in a combined multiomics analysis. We also investigated the effect of PPARα on the polarization fractionation of spinal microglia. RESULTS: PPARα agonist significantly reduce paw withdrawal threshold and paw withdrawal thermal latency, while PPARα antagonist significantly increase paw withdrawal threshold and paw withdrawal thermal latency. 16 S rRNA gene sequencing showed that intraperitoneal injection of GW7647 or GW6471 significantly altered the abundance, homogeneity and composition of the gut microbiome. Analysis of the spinal cord metabolome showed that the levels of spinal cord metabolites were shifted after exposure to GW7647 or GW6471. Alterations in the composition of gut microbiota were significantly associated with the abundance of various spinal cord metabolites. The abundance of Licheniformes showed a significant positive correlation with nicotinamide, benzimidazole, eicosanoids, and pyridine abundance. Immunofluorescence results showed that intraperitoneal injection of GW7647 or GW6471 altered microglial activation and polarization levels. CONCLUSION: Our study shows that PPARα can promote M2-type microglia polarization, as well as alter gut microbiota and metabolites in CCI mice. This study enhances our understanding of the mechanism of PPARα in the treatment of neuropathic pain.

Persistent metabolic toxicities following developmental exposure to hexafluoropropylene oxide trimer acid (HFPO-TA): Roles of peroxisome proliferator activated receptor gamma.

BACKGROUND: Hexafluoropropylene oxide trimer acid (HFPO-TA), a perfluorooctanoic acid (PFOA) substitute, exhibited strong affinity and capability to activate peroxisome proliferator activated receptor gamma (PPARγ), a lipid metabolism regulator, suggesting potential to induce metabolic toxicities. METHODS: Fertile chicken eggs were exposed to 0, 0.5, 1 or 2 mg/kg (egg weight) HFPO-TA and incubated until hatch. Serum from 0- and 3- month-old chickens were subjected to liquid chromatography ultra-high resolution mass spectrometry for HFPO-TA concentration, while liver, pancreas and adipose tissue samples were collected for histopathological assessments. In ovo PPARγ reporter and silencing system were established with lentivirus microinjection. qRT-PCR and immunohistochemistry were utilized to evaluate the expression levels of PPARγ downstream genes. RESULTS: In 3-month-old animals developmentally exposed to HFPO-TA, adipose tissue hyperplasia, hepatic steatosis, pancreas islet hypertrophy and elevated serum free fatty acid / insulin levels were observed. Results of reporter assay and qRT-PCR indicated HFPO-TA-mediated PPARγ transactivation in chicken embryo. Silencing of PPARγ alleviated HFPO-TA-induced changes, while PPARγ agonist rosiglitazone mimicked HFPO-TA-induced effects. qRT-PCR and immunohistochemistry revealed that FASN and GPD1 were upregulated following developmental exposure to HFPO-TA in 3-month-old animals. CONCLUSIONS: Developmental exposure to HFPO-TA induced persistent metabolic toxicities in chickens, in which PPARγ played a central role.

Inter- and trans-generational impacts of real-world PM2.5 exposure on male-specific primary hypogonadism.

Exposure to PM2.5, a harmful type of air pollution, has been associated with compromised male reproductive health; however, it remains unclear whether such exposure can elicit transgenerational effects on male fertility. Here, we aim to examine the effect of paternal exposure to real-world PM2.5 on the reproductive health of male offspring. We have observed that paternal exposure to real-world PM2.5 can lead to transgenerational primary hypogonadism in a sex-selective manner, and we have also confirmed this phenotype by using an external model. Mechanically, we have identified small RNAs (sRNAs) that play a critical role in mediating these transgenerational effects. Specifically, miR6240 and piR016061, which are present in F0 PM sperm, regulate intergenerational transmission by targeting Lhcgr and Nsd1, respectively. We have also uncovered that piR033435 and piR006695 indirectly regulate F1 PM sperm methylation by binding to the 3'-untranslated region of Tet1 mRNA. The reduced expression of Tet1 resulted in hypermethylation of several testosterone synthesis genes, including Lhcgr and Gnas, impaired Leydig cell function and ultimately led to transgenerational primary hypogonadism. Our findings provide insights into the mechanisms underlying the transgenerational effects of paternal PM2.5 exposure on reproductive health, highlighting the crucial role played by sRNAs in mediating these effects. The findings underscore the significance of paternal pre-conception interventions in alleviating the adverse effects of environmental pollutants on reproductive health.

Characterization of Fusarium species causing soybean root rot in Heilongjiang, China, and mechanism underlying the differences in sensitivity to DMI fungicides.

Soybean root rot is a worldwide soil-borne disease threatening soybean production, causing large losses in soybean yield and quality. Fusarium species are the most detrimental pathogens of soybean root rot worldwide, causing large production losses. Fusarium root rot has been frequently reported in Heilongjiang Province of China, but the predominant Fusarium species and the sensitivity of these pathogens to different fungicides remain unclear. In this study, diseased soybean roots were collected from 14 regions of Heilongjiang province in 2021 and 2022. A total of 144 isolates of Fusarium spp. were isolated and identified as seven distinct species: F. scirpi, F. oxysporum, F. graminearum, F. clavum, F. acuminatum, F. avenaceum, and F. sporotrichioide. F. scirpi and F. oxysporum had high separation frequency and strong pathogenicity. The sensitivity of Fusarium spp. to five different fungicides was determined. Mefentrifluconazole and fludioxonil showed good inhibitory effects, and the sensitivity to pydiflumetofen and phenamacril varied between Fusarium species. In particular, the activity of DMI fungicide prothioconazole was lower than that of mefentrifluconazole. Molecular docking showed that mefentrifluconazole mainly bound to CYP51C, but prothioconazole mainly bound to CYP51B. Furthermore, the sensitivity to prothioconazole only significantly decreased in ΔFgCYP51B mutant, and the sensitivity to mefentrifluconazole changed in ΔFgCYP51C and ΔFgCYP51A mutants. The results demonstrated that the predominant Fusarium species causing soybean root rot in Heilongjiang province were F. scirpi and F. oxysporum and DMI fungicides had differences in binding cavity due to the diversity of CYP51 proteins in Fusarium.

Identifying piRNAs that regulate BaP-induced lung injuries: A bottom-up approach from toxicity pathway investigation to animal validation.

PIWI-interacting RNAs (piRNAs) is an emerging class of small non-coding RNAs that has been recently reported to have functions in infertility, tumorigenesis, and multiple diseases in humans. Previously, 5 toxicity pathways were proposed from hundreds of toxicological studies that underlie BaP-induced lung injuries, and a "Bottom-up" approach was established to identify small non-coding RNAs that drive BaP-induced pulmonary effects by investigating the activation of these pathways in vitro, and the expression of the candidate microRNAs were validated in tissues of patients with lung diseases from publications. Here in this study, we employed the "Bottom-up" approach to identifying the roles of piRNAs and further validated the mechanisms in vivo using mouse acute lung injury model. Specifically, by non-coding RNA profiling in in vitro BaP exposure, a total of 3 suppressed piRNAs that regulate 5 toxicity pathways were proposed, including piR-004153 targeting CYP1A1, FGFR1, ITGA5, IL6R, NGRF, and SDHA, piR-020326 targeting CDK6, and piR-020388 targeting RASD1. Animal experiments demonstrated that tail vein injection of respective formulated agomir-piRNAs prior to BaP exposure could all alleviate acute lung injury that was shown by histopathological and biochemical evidences. Immunohistochemical evaluation focusing on NF-kB and Bcl-2 levels showed that exogenous piRNAs protect against BaP-induced inflammation and apoptosis, which further support that the inhibition of the 3 piRNAs had an important impact on BaP-induced lung injuries. This mechanism-driven, endpoint-supported result once again confirmed the plausibility and efficiency of the approach integrating in silico, in vitro, and in vivo evidences for the purpose of identifying key molecules.

miR-145a-5p/SIK1/cAMP-dependent alteration of synaptic structural plasticity drives cognitive impairment induced by coke oven emissions.

Exposure to fine particulate matter (PM) is associated with the neurodegenerative diseases. Coke oven emissions (COEs) in occupational environment are important sources of PM. However, its neurotoxicity is still unclear. Therefore, evaluating the toxicological effects of COE on the nervous system is necessary. In the present study, we constructed mouse models of COE exposure by tracheal instillation. Mice exposed to COE showed signs of cognitive impairment. This was accompanied by a decrease in miR-145a-5p and an increase in SIK1 expression in the hippocampus, along with synaptic structural damage. Our results demonstrated that COE-induced miR-145a-5p downregulation could increase the expression of SIK1 and phosphorylated SIK1, inhibiting the cAMP/PKA/CREB pathway by activating PDE4D, which was associated with reduced synaptic structural plasticity. Furthermore, restoring of miR-145a-5p expression based on COE exposure in HT22 cells could partially reversed the negative effects of COE exposure through the SIK1/PDE4D/cAMP axis. Collectively, our findings link epigenetic regulation with COE-induced neurotoxicity and imply that miR-145a-5p could be an early diagnostic marker for neurological diseases in patients with COE occupational exposure.

Competitive-like binding between carbon black and CTNNB1 to ΔNp63 interpreting the abnormal respiratory epithelial repair after injury.

Airway epithelium is extraordinary vulnerable to damage owning to continuous environment exposure. Subsequent repair is therefore essential to restore the homeostasis of respiratory system. Disruptions in respiratory epithelial repair caused by nanoparticles exposure have been linked to various human diseases, yet implications in repair process remain incompletely elucidated. This study aims to elucidate the key stage in epithelial repair disturbed by carbon black (CB) nanoparticles, highlighting the pivotal role of ΔNp63 in mediating the epithelium repair. A competitive-like binding between CB and beta-catenin 1 (CTNNB1) to ΔNp63 is proposed to elaborate the underlying toxicity mechanism. Specifically, CB exhibits a remarkable inhibitory effect on cell proliferation, leading to aberrant airway epithelial repair, as validated in air-liquid culture. ΔNp63 drives efficient epithelial proliferation during CB exposure, and CTNNB1 was identified as a target of ΔNp63 by bioinformatics analysis. Further molecular dynamics simulation reveals that oxygen-containing functional groups on CB disrupt the native interaction of CTNNB1 with ΔNp63 through competitive-like binding pattern. This process modulates CTNNB1 expression, ultimately restraining proliferation during respiratory epithelial repair. Overall, the current study elucidates that the diminished interaction between CTNNB1 and ΔNp63 impedes respiratory epithelial repair in response to CB exposure, thereby enriching the public health risk assessment on CB-related respiratory diseases.

Plasmodium falciparum selectively degrades α-spectrin of infected erythrocytes after invasion.

Remodeling the erythrocyte membrane and skeleton by the malarial parasite Plasmodium falciparum is closely associated with intraerythrocytic development. However, the mechanisms underlying this association remain unclear. In this study, we present evidence that erythrocytic α-spectrin, but not ß-spectrin, was dynamically ubiquitinated and progressively degraded during the intraerythrocytic development of P. falciparum, from the ring to the schizont stage. We further observed an upregulated expression of P. falciparum phosphatidylinositol 3-kinase (PfPI3K) in the infected red blood cells during the intraerythrocytic development of the parasite. The data indicated that PfPI3K phosphorylated and activated erythrocytic ubiquitin-protein ligase, leading to increased α-spectrin ubiquitination and degradation during P. falciparum development. We further revealed that inhibition of the activity of PfPI3K impaired P. falciparum development in vitro and Plasmodium berghei infectivity in mice. These findings collectively unveil an important mechanism of PfPI3K-ubiquitin-mediated degradation of α-spectrin during the intraerythrocytic development of Plasmodium species. Proteins in the PfPI3K regulatory pathway are novel targets for effective treatment of severe malaria. IMPORTANCE: Plasmodium falciparum is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic α-spectrin is selectively degraded after P. falciparum invasion, while ß-spectrin remained intact. We found that the α-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by P. falciparum phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in P. falciparum-infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs.

Quadratus lumborum block vs. transversus abdominis plane block for postoperative pain control in patients with nephrectomy: A systematic review and network meta-analysis.

STUDY OBJECTIVE: This systematic review and network meta-analysis aimed to compare the analgesic efficacy of transversus abdominis plane block (TAPB) and quadratus lumborum block (QLB) on nephrectomy. DESIGN: Systematic review and network meta-analysis. PATIENTS: Patients undergoing nephrectomy. INTERVENTIONS: TAPB and QLB for postoperative analgesia. MEASUREMENTS: The primary outcome was 24 h morphine-equivalent consumptions after surgery. Secondary outcomes included postoperative pain scores, postoperative opioid consumption, postoperative rescue analgesia, postoperative nausea and vomiting (PONV), length of hospital stay after surgery, and patient satisfaction. MAIN RESULTS: Fourteen studies involving 883 patients were included. Seven studies compared TAPB to control, six studies compared QLB to control, and one study compared TAPB to QLB. For direct meta-analysis of the post-surgical 24 h morphine-equivalent consumption, QLB was lower than control (mean difference [95%CI]: -18.16 [-28.96, -7.37]; I2 = 88%; p = 0.001), while there was no difference between TAPB and control (mean difference [95%CI]: -8.34 [-17.84, 1.17]; I2 = 88%; p = 0.09). Network meta-analysis showed similar findings that QLB was ranked as the best anesthetic technique for reducing postoperative 24 h opioid consumption (p-score = 0.854). Moreover, in direct meta-analysis, as compared to control, the time of first postoperative rescue analgesia was prolonged after QLB (mean difference [95%CI]: 165.00 [128.99, 201.01]; p < 0.00001), but not TAPB (mean difference [95%CI]: 296.82 [-91.92, 685.55]; p = 0.13). Meanwhile, QLB can effectively reduce opioid usages at intraoperative period, as well as at postoperative 6 h and 48 h, while TAPB can only reduce opioid consumption at 6 h after surgery. As compared to control, both TAPB and QLB exhibited the reduction in PONV and pain scores at post-surgical some timepoints. Also, QLB (mean difference [95%CI]: -0.29 [-0.49, -0.08]; p = 0.006) but not TAPB (mean difference [95%CI]: 0.60 [-0.25, 1.45]; p = 0.17) exhibited the shorter postoperative length of hospital stay than control. CONCLUSIONS: QLB is more likely to be effective in reducing postoperative opioid use than TAPB, whereas both of them are superior to control with regard to the reduction in postoperative pain intensity and PONV. TRIAL REGISTRATION: PROSPERO identifier: CRD42022358464.

SPRY1 Deficiency in Keratinocytes Induces Follicular Melanocyte Stem Cell Migration to the Epidermis through p53/Stem Cell Factor/C-KIT Signaling.

The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes (KCs). KCs and melanocytes respond to UV exposure by eliciting a tanning response. However, how KCs and melanocytes interact in the absence of UV exposure is unknown. In this study, we demonstrate that after SPRY1 knockout in epidermal KCs, melanocyte stem cells in the hair follicle exit the niche without depleting the pool of these cells. We also found that melanocyte stem cells migrate to the epidermis in a p53/stem cell factor/C-KIT-dependent manner induced by a tanning-like response resulting from SPRY1 loss in epidermal KCs. Once there, these cells differentiate into functional melanocytes. These findings provide an example in which the migration of melanocyte stem cells to the epidermis is due to loss of SPRY1 in epidermal KCs and show the potential for developing therapies for skin pigmentation disorders by manipulating melanocyte stem cells.

Distributed global output-feedback formation control without velocity measurement for multiple unmanned surface vehicles.

This article studies the distributed formation control problem for multiple unmanned surface vehicles (USVs) considering uncertain coefficient matrixes, unmeasurable velocities, and time-varying disturbances. The main contributions are as follows: First, a global coordinate translation is proposed to partially linearize the nonlinear dynamic model equipped with the unmeasurable velocity. Second, based on the global coordinate translation, a novel type of fixed-time extended two-state observer (FTETSO) is developed to estimate unmeasurable velocities and total disturbances for each vehicle. Wherein, the estimation errors will converge to zero within a fixed time. Meanwhile, considering estimation accuracy, a two-state extension is proposed to replace a single-state extension. Third, using a sliding model-based control technique, an FTETSO-based distributed global output-feedback fixed-time formation controller (GOFFC) is elaborately developed. Based on the proposed controller, the fixed-time convergence of the closed-loop system is ensured. Finally, the validity and stability of the proposed control approach are verified by simulations.

A novel CpG ODN compound adjuvant enhances immune response to spike subunit vaccines of porcine epidemic diarrhea virus.

CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs have been extensively utilized in human vaccines. In our study, we evaluated five B-type CpG ODNs that have stimulatory effects on pigs by measuring the proliferation of porcine peripheral blood mononuclear cells (PBMCs) and assessing interferon gamma (IFN-γ) secretion. Furthermore, this study examined the immunoenhancing effects of the MF59 and CpG ODNs compound adjuvant in mouse and piglet models of porcine epidemic diarrhea virus (PEDV) subunit vaccine administration. The in vitro screening revealed that the CpG ODN named CpG5 significantly stimulated the proliferation of porcine PBMCs and elevated IFN-γ secretion levels. In the mouse vaccination model, CpG5 compound adjuvant significantly bolstered the humoral and cellular immune responses to the PEDV subunit vaccines, leading to Th1 immune responses characterized by increased IFN-γ and IgG2a levels. In piglets, the neutralizing antibody titer was significantly enhanced with CpG5 compound adjuvant, alongside a considerable increase in CD8+ T lymphocytes proportion. The combination of MF59 adjuvant and CpG5 exhibits a synergistic effect, resulting in an earlier, more intense, and long-lasting immune response in subunit vaccines for PEDV. This combination holds significant promise as a robust candidate for the development of vaccine adjuvant.

Carboxyl-Decorated UiO-66 Supporting Pd Nanoparticles for Efficient Room-Temperature Hydrodeoxygenation of Lignin Derivatives.

Hydrodeoxygenation (HDO) of lignin derivatives at room-temperature (RT) is still of challenge due to the lack of satisfactory activity reported in previous literature. Here, it is successfully designed a Pd/UiO-66-(COOH)2 catalyst by using UiO-66-(COOH)2 as the support with uncoordinated carboxyl groups. This catalyst, featuring a moderate Pd loading, exhibited exceptional activity in RT HDO of vanillin (VAN, a typical model lignin derivative) to 2-methoxyl-4-methylpheonol (MMP), and >99% VAN conversion with >99% MMP yield is achieved, which is the first metal-organic framework (MOF)-based catalyst realizing the goal of RT HDO of lignin derivatives, surpassing previous reports in the literature. Detailed investigations reveal a linear relationship between the amount of uncoordinated carboxyl group and MMP yield. These uncoordinated carboxyl groups accelerate the conversion of intermediate such as vanillyl alcohol (VAL), ultimately leading to a higher yield of MMP over Pd/UiO-66-(COOH)2 catalyst. Furthermore, Pd/UiO-66-(COOH)2 catalyst also exhibits exceptional reusability and excellent substrate generality, highlighting its promising potential for further biomass utilization.

Biologics protect psoriasis patients from being exacerbated by COVID-19 infection.

Background: Patients with psoriasis may experience an exacerbation in symptoms following COVID-19 infection. After abandoning 'zero COVID' strategies, China experienced a surge of Omicron infections. Objectives: We aimed to investigate psoriasis exacerbation in psoriatic patients with COVID-19, following treatment with three different biologics, adalimumab, secukinumab, and ixekizumab. Methods: We performed a prospective study (n = 209) at our hospital between November 01, 2022, and February 15, 2023. We defined △ PASI as post-COVID-19 PASI minus pre-COVID-19 PASI. Two endpoints were set in this study. △ PASI >0 was defined as exacerbation of psoriasis after infection. △ PASI >3 was defined as a severe exacerbation of psoriasis symptoms after infection. In addition, serum OAS1, OAS2, and OAS3 were also assessed. Results: Results showed that the severity of psoriasis can worsen after COVID-19 infection, and a smaller proportion of patients taking biologics developed worsening psoriasis compared to those not using biologics; however, only the patients taking ixekizumab demonstrated a statistically significant difference (p < 0.05), while those taking adalimumab or secukinumab didn't. What's more, the use of biological agents suppressed the serum OAS2 and OAS3 at low levels and elevated the serum OAS1 level in patients with psoriasis. Conclusions: This study provided new insights into the protective role of biological agents in patients with psoriasis who were infected with COVID-19, and we proposed that psoriatic patients treated with biologics should continue with the treatment during the COVID-19 pandemic.