Far-UVC (UV222) based photolysis, photooxidation, and photoreduction of chlorophenols using a KrCl-excimer lamp: Degradation, dechlorination, and detoxification.

The KrCl-excimer lamp, emitting far-UVC light at 222 nm (UV222), offers a promising alternative to conventional UVC light at 254 nm (UV254) for the photolysis of organic pollutants and the activation of radical sensitizers. This study was aimed to investigate the efficiencies of UV222 in the treatment of halogenated aromatics, focusing on its performance in degradation, dechlorination and detoxification. Chlorophenols, representative recalcitrant and toxic halogenated aromatics, were used as target pollutants. The pathways of direct photolysis, photooxidation and photoreduction under UV222 illumination were compared. UV222 outperformed UV254 in photolyzing chlorophenols (1.4-34.1 times faster), especially protonated chlorophenols, due to substantially higher UV absorption (17.1-108.0 times) and quantum yields (2.1-3.4 times). The quantum yields of chlorophenols were influenced by the inducive electron-withdrawing effect of Cl-substitutes. Moreover, UV222 improved the dechlorination of chlorophenols to 95 % compared to 60 % by UV254. The introduction of radical sensitizer (e.g., H2O2, nitrate, and sulfite) reduced 4-chlorophenol photolysis by competing for UV222 absorption, though the sensitizers partially increased radical oxidation via generating •OH or eaq-. UV222 photolysis of 4-chlorophenol increased the toxicity by 88.6 times through forming toxic intermediates (e.g., hydroquinone and resorcinol). Notably, •OH and eaq- (i.e., UV222/H2O2 and UV222/sulfite) increased the dechlorination and •OH (i.e., UV222/H2O2) detoxified the mixture solution. Moreover, UV222 photolysis remained effective for 4-chlorophenol removal in real paper-mill wastewater, indicating the potential application of KrCl* lamp UV222.

Efficient Electrocatalytic Hydrodechlorination and Detoxification of Chlorophenols by Palladium-Palladium Oxide Heterostructure.

Electrocatalytic hydrodechlorination is a promising approach for simultaneous pollutant purification and valorization. However, the lack of electrocatalysts with high catalytic activity and selectivity limits its application. Here, we propose a palladium-palladium oxide (Pd-PdO) heterostructure for efficient electrocatalytic hydrodechlorination of recalcitrant chlorophenols and selective formation of phenol with superior Pd-mass activity (1.35 min-1 mgPd-1), which is 4.4 times of commercial Pd/C and about 10-100 times of reported Pd-based catalysts. The Pd-PdO heterostructure is stable in real water matrices and achieves selective phenol recovery (>99%) from the chlorophenol mixture and efficient detoxification along chlorophenol removal. Experimental results and computational modeling reveal that the adsorption/desorption behaviors of zerovalent Pd and PdO sites in the Pd-PdO heterostructure are optimized and a synergy is realized to promote atomic hydrogen (H*) generation, transfer, and utilization: H* is efficiently generated at zerovalent Pd sites, transferred to PdO sites, and eventually consumed in the dechlorination reaction at PdO sites. This work provides a promising strategy to realize the synergy of Pd with different valence states in the metal-metal oxide heterostructure for simultaneous decontamination, detoxification, and resource recovery from halogenated organic pollutants.

Assessing excimer far-UVC (222 nm) irradiation for advanced oxidation processes: Oxidants photochemistry and micropollutants degradation.

The KrCl* excimer lamp (UV222) is a promising alternative of low-pressure mercury lamp (UV254) for UV-based advanced oxidation processes (UV-AOPs), because it is mercury-free and has high photon energy. But there lacks a comprehensive assessment of UV222-AOPs based on different radicals. Herein, the properties (e.g., oxidant decay and innate radical quantum yield), and micropollutant degradation, were comprehensively studied for representative oxidants (i.e., hydrogen peroxide, persulfate (PDS), monochloramine, and free active chlorine (FAC)) under UV222 irradiation. UV222 outperformed UV254 for the activation of oxidants with 2.6-14.4 times fluence-based kinetic constant (kF). The main reason of enhanced activation varied with oxidants: higher UV absorbance for H2O2, higher innate quantum yield for monochloramine and FAC, and both reasons for PDS. Overall, PDS was the optimum oxidant under UV222 for the degradation of 8 representative micropollutants because of effective promotion of radical formation, as confirmed by radical competitive kinetics and modeling simulations. In real water, UV222/PDS still show advantages than UV254/PDS in terms of micropollutant elimination efficacy (3.2-5.3 times) and energy consumption (33.9 %-57.6 % lower) though it was more inhibited by water constituents via competing for UV222 photons. This study fills gaps in photochemistry knowledge and will facilitate engineering practice of UV222-AOPs.

Increased formation of brominated disinfection by-products and toxicities during low-H2O2-mediated ozonation of reclaimed water.

Reusing reclaimed water requires stringent disinfection but inevitably generates disinfection by-products (DBPs). H2O2/O3 treatment is an efficient and environmentally benign disinfection method. For the first time, our bioassay results elucidate that low H2O2/O3 ratio (molar) treated water increased unignorable toxicity effect compared to that of the high H2O2/O3 ratio. To clarify this finding, individual organic brominated DBPs (Br-DBPs), bromate, and adsorbable organic bromine (AOBr) were considered due to their potential risk. Organic Br-DBPs were mainly generated from ozone-induced pathways. Individual organic Br-DBPs were not the primary concern in this scenario because they are typically only produced in observable quantities at bromide concentrations exceeding 500 µg/L, and even then, they often remain below detection limits when treated with H2O2/O3. On the contrary, both bromate and AOBr were detectable at low H2O2/O3 ratios. Furthermore, bromate is produced from HOBr and bromine radicals induced by HO•. Moreover, bromate formation was promoted because of increased HO• formation, particularly at H2O2/O3 ratios <0.24. To prevent HO•-induced pathways from being dominant, higher H2O2/O3 ratios (>0.48) were required. Toxicity assays revealed that AOBr-included organic extracts of ozonated reclaimed water induced more toxic effects. The toxicity induced by the organic fraction resulted from its decreased oxidation level, which was, in turn, driven by the increased formation of bromate. Enhanced toxicity effects were observed when cells were exposed to a bromate and organic extract mixture. It indicates that both the AOBr and bromate present in low-H2O2-O3-treated reclaimed water pose potential risks, and their coexistence further elevates these risks. Increasing the H2O2/O3 ratio markedly decreased the generation of intracellular oxidative substances and oxidative damage. In conclusion, when treated with H2O2/O3, shifting from HO•-induced pathways to ozone-induced pathways by a relatively high H2O2/O3 ratio decreased the amounts of DBPs produced and controlled the toxic effects to ensure the safety of ozonated reclaimed water.

Aß25-35-induced autophagy and apoptosis are prevented by the CRMP2-derived peptide ST2-104 (R9-CBD3) via a CaMKKß/AMPK/mTOR signaling hub.

We previously reported that the peptide ST2-104 (CBD3, for Ca2+ channel-binding domain 3), derived from the collapsin response mediator protein 2 (CRMP2)-a cytosolic phosphoprotein, protects neuroblastoma cells against ß-amyloid (Aß) peptide-mediated toxicity through engagement of a phosphorylated CRMP2/NMDAR pathway. Abnormal aggregation of Aß peptides (e.g., Aß25-35) leads to programmed cell death (apoptosis) as well autophagy-both of which contribute to Alzheimer's disease (AD) progression. Here, we asked if ST2-104 affects apoptosis and autophagy in SH-SY5Y neuroblastoma challenged with the toxic Aß25-35 peptide and subsequently mapped the downstream signaling pathways involved. ST2-104 protected SH-SY5Y cells from death following Aß25-35 peptide challenge by reducing apoptosis and autophagy as well as limiting excessive calcium entry. Cytotoxicity of SHY-SY5Y cells challenged with Aß25-35 peptide was blunted by ST2-104. The autophagy activator Rapamycin blunted the anti-apoptotic activity of ST2-104. ST2-104 reversed Aß25-35-induced apoptosis via inhibiting Ca2+/CaM-dependent protein kinase kinase ß (CaMKKß)-mediated autophagy, which was partly enhanced by STO-609 (an inhibitor of CaMKKß). ST2-104 attenuated neuronal apoptosis by inhibiting autophagy through a CaMKKß/AMPK/mTOR signaling hub. These findings identify a mechanism whereby, in the face of Aß25-35, the concerted actions of ST2-104 leads to a reduction in intracellular calcium overload and inhibition of the CaMKKß/AMPK/mTOR pathway resulting in attenuation of autophagy and cellular apoptosis. These findings define a mechanistic framework for how ST2-104 transduces "outside" (calcium channels) to "inside" signaling (CaMKKß/AMPK/mTOR) to confer neuroprotection in AD.

Diverse Head-to-Tail Sequences in the Circular Genome of Human Bocavirus Genotype 1 among Children with Acute Respiratory Infections Implied the Switch of Template Chain in the Rolling-Circle Replication Model.

Head-to-tail sequences have been reported in human bocavirus (HBoV) 1-4. To reveal their features and functions, HBoV DNA was screened among respiratory specimens from pediatric patients with an acute respiratory infection (ARI) between April 2020 and December 2022, followed by HBoV genotyping. Head-to-tail sequences were detected using nested PCR, TA cloning, and Sanger sequencing, and these findings were confirmed by mNGS and amplicon sequencing. The secondary structure was predicted using the Mfold web server. The results indicated that head-to-tail sequences were detected in 42 specimens through TA cloning from 351 specimens positive for HBoV1 DNA, yielding 92 sequences into 32 types and 2 categories. Additionally, head-to-tail sequences were detected in 16 specimens by amplicon sequencing, yielding 60 sequences categorized into 23 types. The 374nt type, detected in 13 specimens, contains variants 374a and 374b, which differ in the unpaired loop regions of the palindrome or complementary reverse sequences, implying a switch of template chains during the replication process. The mNGS results in three specimens confirmed the presence of circular genome in copies below 1%. In conclusion, head-to-tail sequences of HBoV1 were common in children with ARI and were highly diverse in length and sequences. The variants may be generated by the switch of the template chain in the rolling-circle replication model.

A harsh environmental resistant and long-term stable ionic conductive hydrogel by one-step preparation for wireless health activity and physiological state detection.

Benefiting from the good electromechanical performance, ionic conductive hydrogel can easily convert the deformation into electrical signals, showing great potential in wearable electronic devices. However, due to the high water content, icing and water evaporation problems seriously limit their development. Although additives can ease these disadvantages, the accompanying performance degradation and complex preparation processes couldn't meet application needs. In this work, a convenient method was provided to prepare ionic conductive hydrogels with sensitive electromechanical performance, harsh environmental tolerance, and long-term stability without additives. Based on the hydratability between metal ions and water molecules resulting in spatial condensation of the hydrogel framework, the hydrogel exhibits good flexibility and ionic conductivity (70.3 mS/cm). Furthermore, the metal salt can bind with water molecules to reduce the vapor pressure, thus endowing the hydrogel with good freezing resistance (-40 °C) and long-term stability over a wide temperature range (-20 °C-50 °C). Based on these unique advantages, the hydrogel shows good sensitivity. Even in a harsh environment, it still maintained excellent stability (-20 °C-50 °C, GF = 2.2, R2 > 0.99). Assembled with a Wi-Fi device, the hydrogel sensor demonstrates good health activity and physiological state detection performance, demonstrating great potential for wearable medical devices.

Prevalence of nonalcoholic fatty liver disease in patients with hepatitis B: A meta-analysis.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has increased in recent clinical practice; however, the relationship between CHB and hepatic steatosis (HS) remains controversial. AIM: To shed light on the potential association between NAFLD and hepatitis B virus (HBV) infection. METHODS: We conducted a systematic literature search using multiple databases, including PubMed, the Cochrane Library, Web of Science, and EMBASE, to identify relevant studies. Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis. RESULTS: Comprehensive meta-analysis software was used for statistical analysis, which covered 20 studies. The results indicated a lower NAFLD susceptibility in HBV-infected individuals (pooled OR = 0.87; 95%CI = 0.69-1.08; I 2 = 91.1%), with diabetes (P = 0.015), body mass index (BMI; P = 0.010), and possibly age (P = 0.061) as heterogeneity sources. Of note, in four studies (6197 HBV patients), HBV-infected individuals had a reduced NAFLD risk (OR = 0.68, 95%CI = 0.51-0.89, P = 0.006). A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients, along with specific biochemical indicators, including BMI, creatinine, uric acid, fasting blood glucose, and homeostasis model assessment of insulin resistance. CONCLUSION: HBV infection may provide protection against HS; however, the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters.

Predicting protein conformational motions using energetic frustration analysis and AlphaFold2.

Proteins perform their biological functions through motion. Although high throughput prediction of the three-dimensional static structures of proteins has proved feasible using deep-learning-based methods, predicting the conformational motions remains a challenge. Purely data-driven machine learning methods encounter difficulty for addressing such motions because available laboratory data on conformational motions are still limited. In this work, we develop a method for generating protein allosteric motions by integrating physical energy landscape information into deep-learning-based methods. We show that local energetic frustration, which represents a quantification of the local features of the energy landscape governing protein allosteric dynamics, can be utilized to empower AlphaFold2 (AF2) to predict protein conformational motions. Starting from ground state static structures, this integrative method generates alternative structures as well as pathways of protein conformational motions, using a progressive enhancement of the energetic frustration features in the input multiple sequence alignment sequences. For a model protein adenylate kinase, we show that the generated conformational motions are consistent with available experimental and molecular dynamics simulation data. Applying the method to another two proteins KaiB and ribose-binding protein, which involve large-amplitude conformational changes, can also successfully generate the alternative conformations. We also show how to extract overall features of the AF2 energy landscape topography, which has been considered by many to be black box. Incorporating physical knowledge into deep-learning-based structure prediction algorithms provides a useful strategy to address the challenges of dynamic structure prediction of allosteric proteins.

Mechanism underlying the effects of exercise against type 2 diabetes: A review on research progress.

Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes (T2D) in certain nations. The present report summarizes the latest findings from the research on the beneficial effect of exercise on T2D. The objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D, in addition to identify the limitations of the existing literature, thereby provide direction for future research in this field.

Multiple Roles of Anions on the Degradation Efficiency and Mineralization Pathway of Recalcitrant Acetaldehyde by Vacuum Ultraviolet (185 nm) Oxidation.

Vacuum-UV (185 nm, VUV) is widely applied to polish reverse osmosis permeate (ROP), such as the production of electronics-grade ultrapure water. In this study, the VUV oxidation of acetaldehyde, a common carbonyl in ROP, was found to be influenced by anions even at low concentrations. Interestingly, the influencing extent and mechanism varied depending on the anions. Bicarbonate minimally affected the VUV-photon absorption and •OH consumption, but at 5000 µg-C·L-1, it decreased the degradation of acetaldehyde by 58.7% possibly by scavenging organic radicals or other radical chain reactions. Nitrate strongly competed for VUV-photon absorption and •OH scavenging through the formation of nitrite, and at 500 µg-N·L-1, it decreased the removal rate of acetaldehyde degradation by 71.2% and the mineralization rate of dissolved organic carbon by 53.4%. Chloride competed for VUV-photon absorption and also generated reactive chlorine species, which did not affect acetaldehyde degradation but influenced the formation of organic byproducts. The radical chain reactions or activation of anions under VUV irradiation could compensate for the decrease in oxidation performance and need further investigation. In real ROPs, the VUV oxidation of acetaldehyde remained efficient, but mineralization was hindered due to nitrate and chloride anions. This study deepens the understanding of the photochemistry and feasibility of VUV in water with low concentrations of anions.

Combined maternal KIR2DL4 and fetal HLA-G polymorphisms were associated with preeclampsia in a Han Chinese population.

Preeclampsia is the main cause of maternal and infant mortality and morbidity during pregnancy. Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) and human leukocyte antigen G (HLA-G) play crucial roles in immune tolerance at the maternal-fetal interface. In this case‒control study, 154 maternal-fetal pairs were recruited, including 74 pairs with preeclampsia (56 of 74 pairs from family triads) and 80 pairs with a normal pregnancy (78 of 80 pairs from family triads). SNaPshot technology was used to detect genetic polymorphisms for 7 TagSNPs in the KIR2DL4 and HLA-G genes. Among the fetal HLA-G gene polymorphisms, rs9380142 (A vs. G: OR = 2.802, 95% CI = 1.761-4.458) and rs1063320 (G vs. C: OR = 1.807, 95% CI = 1.144-2.852) differed between the preeclampsia group and the control group. The transmission disequilibrium test (TDT) suggested that the differences in the rs9380142G/A polymorphism in foetuses between preeclampsia triads and control triads were due to differences in transmission from the parents (P = 0.001). There was no significant difference in the distribution of maternal KIR2DL4 alleles or genotype frequency between the preeclampsia group and the control group. Gene‒gene interaction analysis revealed that the combined genotypes of maternal rs649216-CC and fetal rs9380142-GG, maternal rs1051456-CG/GG and fetal rs9380142-GG, maternal rs34785252-CC and fetal rs9380142-AA/GA, and maternal rs34785252-CC/AA and fetal rs9380142-GG were associated with a significantly lower risk of preeclampsia. Therefore, this study suggested that the combination of maternal KIR2DL4 and fetal HLA-G polymorphisms was associated with preeclampsia in a Han Chinese population.

Metagenomics reveals the potential transmission risk of resistomes from urban park environment to human.

Urban parks play a significant role in urban ecosystems and are strongly associated with human health. Nevertheless, the biological contamination of urban parks - opportunistic pathogens and antibiotic resistance genes (ARGs) - has been poorly reported. Here, metagenomic and 16 S rRNA sequencing methods were used to study the distribution and assembly of opportunistic pathogens and ARGs in soil and water from nine parks in Lanzhou city, and further compared them with local human gut microbiomes to investigate the potential transmission risk. Our results revealed that the most important type of drug resistance in urban parks was multidrug resistance, with various resistance mechanisms. Approximately half of ARGs were shared between human gut and park environment, and it was noteworthy that cross-species transmission might exist among some high-risk ARGs, such as mepA and mdtE, with a significant enrichment in human gut. Metagenomic binning uncovered several bacterial genomes carrying adjacent ARGs, MGEs, and virulence genes, indicating a possibility that these genes may jointly transfer among different environments, particularly from park environment to human. Our results provided a reference point for the management of environmental pollutants in urban parks.

Therapeutic expression of RAS Degrader RRSP in Pancreatic Cancer via Nanocarrier-mediated mRNA delivery.

About one-third of all human cancers encode abnormal RAS proteins locked in a constitutively activated state to drive malignant transformation and uncontrolled tumor growth. Despite progress in development of small molecules for treatment of mutant KRAS cancers, there is a need for a pan-RAS inhibitor that is effective against all RAS isoforms and variants and that avoids drug resistance. We have previously shown that the naturally occurring bacterial enzyme RAS/RAP1-specific endopeptidase (RRSP) is a potent RAS degrader that can be re-engineered as a biologic therapy to induce regression of colorectal, breast, and pancreatic tumors. Here, we have developed a strategy for in vivo expression of this RAS degrader via mRNA delivery using a synthetic nonviral gene delivery platform composed of the poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) block copolymer conjugated to a dendritic cationic peptide (PPDP2). Using this strategy, PPDP2 is shown to deliver mRNA to both human and mouse pancreatic cells resulting in RRSP gene expression, activity, and loss of cell proliferation. Further, pancreatic tumors are reduced with residual tumors lacking detectable RAS and phosphorylated ERK. These data support that mRNA-loaded synthetic nanocarrier delivery of a RAS degrader can interrupt the RAS signaling system within pancreatic cancer cells while avoiding side effects during therapy.

HT-NMR Studies of the Be-F Coordination Structure in FNaBe and FLiBe Mixed Salts.

Molten NaF-BeF2 salt is widely considered a promising candidate to replace FLiBe in molten salt reactor applications, which is crucial to reducing the operating costs of the molten salt reactor. Studies on beryllium compounds are rarely conducted due to their volatility and high toxicity. Herein, the Be-F coordination structure of NaF/BeF2 mixed salts was investigated in-depth through various HT-NMR and solid-state NMR methods, which are optimized to be appropriate for the detection of beryllium compounds. It was found that Na2BeF4 and NaBeF3 crystals were transformed into amorphous tetrahedral coordinated networks when there was an increase in the BeF2 concentration in the mixed salts. The main coordinate structure comparisons between FNaBe and FLiBe were analyzed, which exhibit high similarity due to the covalent effect of Be-F bonding, demonstrating the theoretical feasibility of applying FNaBe salts as a substitute for FLiBe in MSR systems. In addition, the transition from the crystal phase to the amorphous phase occurred at a lower BeF2 concentration for FNaBe than that for FLiBe. This was further verified by the results of ab initio molecular dynamics (AIMD) simulation that FNaBe melts had more disordered structures, thus causing slight changes in their physical properties.

Armillariella tabescens-derived polysaccharides alleviated â±°-Gal-induced neuroinflammation and cognitive injury through enterocerebral axis and activation of keap-1/Nrf2 pathway.

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.

Relationship between atherosclerotic burden and depressive symptoms in hypertensive patients: A cross-sectional study based on the NHANES database.

OBJECTIVE: The relationship between atherosclerotic burden, depressive symptoms, and clinically relevant depression (CRD) in hypertensive patients is unclear. In this study, we used the atherosclerotic index of plasma (AIP) to quantify atherosclerotic burden and explore its association with depressive symptoms and CRD in hypertensive patients. METHODS: Hypertension-diagnosed patients were extracted from the National Health and Nutrition Examination Survey (NHANES) database. The relationships between AIP and depressive symptoms and CRD risk in patients were examined through the weighted logistic regression and the weighted linear regression models. Restrictive cubic spline curves were employed to analyze potential nonlinear associations between AIP and outcome indicators. Additionally, subgroup analyses and intergroup interaction tests were conducted. RESULTS: The AIP was considerably associated with the severity of depressive symptoms in hypertensive patients, according to the findings of weighted linear regression. Weighted logistic regression analysis showed that high AIP was significantly associated with a high risk of clinically relevant depression in hypertensive patients. This trend was consistent across various subgroups within the population. CONCLUSION: AIP was observed to be a significant risk factor for clinically relevant depression in hypertensive patients. Atherosclerotic burden in hypertensive patients was significantly associated with the severity of their depressive symptoms.

Unveiling immune tolerance pathways in preeclampsia placenta: implications for molecular targets and discovery of potential biomarkers.

During pregnancy, there is a link between disruption of maternal immune tolerance and preeclampsia, but the molecular mechanisms that regulate maternal and fetal immune tolerance remain unclear. This study employs bioinformatics to identify new markers related to placental immune tolerance and explore their potential role in predicting preeclampsia. Analyzing preeclampsia-related gene expression profiles in the Gene Expression Omnibus (GEO) dataset reveals 211 differentially expressed genes (DEGs) in the placenta, mainly influencing immune cell differentiation and response pathways. Employing weighted gene co-expression network analysis (WGCNA) and lasso regression, four potential target genes (ANKRD37, CRH, LEP, SIGLEC6) are identified for potential prediction of preeclampsia. Validation using the GSE4707 dataset confirmed the diagnostic and predictive potential of these candidate genes. RT-qPCR verified up-regulation in the placenta, while ELISA showed their correlation with immune tolerance factors associated with placental immune tolerance. As a result of this study, identifies potential biomarkers associated with placental immunity and contributes to understanding the molecular mechanism of preeclampsia.

A Biomimetic Multi-Component Subunit Vaccine via Ratiometric Loading of Hierarchical Hydrogels.

The development of subunit vaccines that mimic the molecular complexity of attenuated vaccines has been limited by the difficulty of intracellular co-delivery of multiple chemically diverse payloads at controllable concentrations. We report on hierarchical hydrogel depots employing simple poly(propylene sulfone) homopolymers to enable ratiometric loading of a protein antigen and four physicochemically distinct adjuvants in a hierarchical manner. The optimized vaccine consisted of immunostimulants either adsorbed to or encapsulated within nanogels, which were capable of noncovalent anchoring to subcutaneous tissues. These 5-component nanogel vaccines demonstrated enhanced humoral and cell-mediated immune responses compared to formulations with standard single adjuvant and antigen pairing. The use of a single simple homopolymer capable of rapid and stable loading and intracellular delivery of diverse molecular cargoes holds promise for facile development and optimization of scalable subunit vaccines and complex therapeutic formulations for a wide range of biomedical applications.

Lysine Methyltransferase 5A Promotes the Progression of Growth Hormone Pituitary Neuroendocrine Tumors through the Wnt/ß-Catenin Signaling Pathway.

INTRODUCTION: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. METHODS: Immunohistochemistry, qRT-PCR, and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. RESULTS: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation, and FCM assays. Additionally, WB analysis identified the Wnt/ß-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. CONCLUSION: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/ß-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs.