ALKBH5 targets ACSL4 mRNA stability to modulate ferroptosis in hyperbilirubinemia-induced brain damage.

Bilirubin-induced brain damage is a serious clinical consequence of hyperbilirubinemia, yet the underlying molecular mechanisms remain largely unknown. Ferroptosis, an iron-dependent cell death, is characterized by iron overload and lipid peroxidation. Here, we report a novel regulatory mechanism of demethylase AlkB homolog 5 (ALKBH5) in acyl-coenzyme A synthetase long-chain family member 4 (ACSL4)-mediated ferroptosis in hyperbilirubinemia. Hyperdifferential PC12 cells and newborn Sprague-Dawley rats were used to establish in vitro and in vivo hyperbilirubinemia models, respectively. Proteomics, coupled with bioinformatics analysis, first suggested the important role of ferroptosis in hyperbilirubinemia-induced brain damage. In vitro experiments showed that ferroptosis is activated in hyperbilirubinemia, and ferroptosis inhibitors (desferrioxamine and ferrostatin-1) treatment effectively alleviates hyperbilirubinemia-induced oxidative damage. Notably, we observed that the ferroptosis in hyperbilirubinemia was regulated by m6A modification through the downregulation of ALKBH5 expression. MeRIP-seq and RIP-seq showed that ALKBH5 may trigger hyperbilirubinemia ferroptosis by stabilizing ACSL4 mRNA via m6A modification. Further, hyperbilirubinemia-induced oxidative damage was alleviated through ACSL4 genetic knockdown or rosiglitazone-mediated chemical repression but was exacerbated by ACSL4 overexpression. Mechanistically, ALKBH5 promotes ACSL4 mRNA stability and ferroptosis by combining the 669 and 2015 m6A modified sites within 3' UTR of ACSL4 mRNA. Our findings unveil a novel molecular mechanism of ferroptosis and suggest that m6A-dependent ferroptosis could be an underlying clinical target for the therapy of hyperbilirubinemia.

Dysregulated serum lipid profile is associated with inflammation and disease activity in primary Sjögren's syndrome: a retrospective study in China.

PURPOSE: To investigate the relationship between the lipid profiles of patients with primary Sjögren's syndrome (pSS) and other clinical characteristics, laboratory examination, disease activity, and inflammatory factors. In addition, the risk factors for hyperlipidemia-related complications of pSS and the effect of hydroxychloroquine (HCQ) usage on the lipid profile were incorporated into this study. METHODS: This is a single-center, retrospective study that included 367 patients who were diagnosed with pSS at Tongji Hospital, School of Medicine, Tongji University, China from January 2010 to March 2022. Initially, demographic information, clinical characteristics, medication records, and complications of the patients were gathered. A case-control analysis compared the 12 systems involvement (ESSDAI domain), clinical symptoms, and laboratory tests between pSS patients with and without dyslipidemia. A simple linear regression model was employed to investigate the relationship between serum lipid profile and inflammatory factors. Logistics regression analysis was performed to assess variables for hyperlipidemia-related complications of pSS. The paired t-test was then used to evaluate the improvement in lipid profile among pSS patients. RESULTS: 48.7 % of all pSS patients had dyslipidemia, and alterations in lipid levels were related to gender, age, and smoking status but not body mass index (BMI). Dyslipidemia is more prevalent in pSS patients who exhibit heightened autoimmunity and elevated levels of inflammation. Higher concentrations of multiple highly inflammatory factors correlate with a more severe form of dyslipidemia. Non-traditional cardiovascular risk factors may contribute to hyperlipidemia-related complications of pSS, such as increased, low complement 3 (C3) and low C4. According to our study, HCQ usage may protect against lipid-related disease in pSS. CONCLUSION: Attention should be paid to the dyslipidemia of pSS. This research aims to clarify the population portrait of pSS patients with abnormal lipid profiles and provides insights into the correlation between metabolism and inflammation in individuals with pSS and the potential role they play in the advancement of the disease. These findings provide novel avenues for further understanding the underlying mechanisms of pSS pathogenesis.

Ferroptosis contributes to hemolytic hyperbilirubinemia­induced brain damage in vivo and in vitro.

Ferroptosis is driven by iron­dependent accumulation of lipid hydroperoxides, and hemolytic hyperbilirubinemia causes accumulation of unconjugated bilirubin and iron. The present study aimed to assess the role of ferroptosis in hemolytic hyperbilirubinemia­induced brain damage (HHIBD). Rats were randomly divided into the control, phenylhydrazine (PHZ) and deferoxamine (DFO) + PHZ groups, with 12 rats in each group. Ferroptosis­associated biochemical and protein indicators were measured in the brain tissue of rats. We also performed tandem mass tag­labeled proteomic analysis. The levels of iron and malondialdehyde were significantly higher and levels of glutathione (GSH) and superoxide dismutase activity significantly lower in the brain tissues of the PHZ group compared with those in the control group. HHIBD also resulted in significant increases in the expression of the ferroptosis­related proteins acyl­CoA synthetase long­chain family member 4, ferritin heavy chain 1 and transferrin receptor and divalent metal transporter 1, as well as a significant reduction in the expression of ferroptosis suppressor protein 1. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that the differentially expressed proteins of rat brain tissues between the control and PHZ groups were significantly involved in ferroptosis, GSH metabolism and fatty acid biosynthesis pathways. Pretreatment with DFO induced antioxidant activity and alleviated lipid peroxidation­mediated HHIBD. In addition, PC12 cells treated with ferric ammonium citrate showed shrinking mitochondria, high mitochondrial membrane density, and increased lipid reactive oxygen species and intracellular ferrous iron, which were antagonized by pretreatment with ferrostatin­1 or DFO, which was reversed by pretreatment with ferrostatin­1 or DFO. The present study demonstrated that ferroptosis is involved in HHIBD and provided novel insights into candidate proteins that are potentially involved in ferroptosis in the brain during hemolytic hyperbilirubinemia.

Chronic Epstein-Barr virus infection: A potential junction between primary Sjögren's syndrome and lymphoma.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that targets exocrine glands, leading to exocrine dysfunction. Due to its propensity to infect epithelial and B cells, Epstein-Barr virus (EBV) is hypothesized to be related with pSS. Through molecular mimicry, the synthesis of specific antigens, and the release of inflammatory cytokines, EBV contributes to the development of pSS. Lymphoma is the most lethal outcome of EBV infection and the development of pSS. As a population-wide virus, EBV has had a significant role in the development of lymphoma in people with pSS. In the review, we will discuss the possible causes of the disease.

The interplay between lncRNA NR_030777 and SF3B3 in neuronal damage caused by paraquat.

Paraquat (PQ) has been widely acknowledged as an environmental risk factor for Parkinson's disease (PD). However, the interaction between splicing factor and long non-coding RNA (lncRNA) in the process of PQ-induced PD has rarely been studied. Based on previous research, this study focused on splicing factor 3 subunit 3 (SF3B3) and lncRNA NR_030777. After changing the target gene expression level by lentiviral transfection technology, the related gene expression was detected by western blot and qRT-PCR. The expression of SF3B3 protein was reduced in Neuro-2a cells after PQ exposure, and the reactive oxygen species (ROS) scavenger N-acetylcysteine prevented this decline. Knockdown of SF3B3 reduced the PQ-triggered NR_030777 expression increase, and overexpression of NR_030777 reduced the transcriptional and translational level of Sf3b3. Then, knockdown of SF3B3 exacerbated the PQ-induced decrease in cell viability and aggravated the reduction of tyrosine hydroxylase (TH) protein expression. Overexpressing SF3B3 reversed the reduction of TH expression caused by PQ. Moreover, after intervention with the autophagy inhibitor Bafilomycin A1, LC3B-II protein expression was further increased in Neuro-2a cells with the knockdown of SF3B3, indicating that autophagy was enhanced. In conclusion, PQ modulated the interplay between NR_030777 and SF3B3 through ROS production, thereby impairing autophagic flux and causing neuronal damage.

Osteoarthritis or arthritis? Toward understanding of primary Sjögren's syndrome patients with arthralgia.

OBJECTIVE: To identify primary Sjögren's syndrome (pSS) patients with arthralgia at risk for osteoarthritis (OA) or arthritis. METHODS: This study included 368 pSS patients admitted to a mono-centric from March 2010 to December 2020. Patients were divided into groups according to whether complicated with OA or arthritis. Data were analyzed to determine the differences in demographical characteristics, symptoms, and laboratory examination. RESULTS: The involvement of the OA joints was predominately knee and spine sites (including cervical and lumbar spine degeneration). When diagnosing arthritis, it was mainly peripheral symmetric polyarthritis, the most affected sites were the interphalangeal and metacarpophalangeal joints. There were significant differences in age, disease duration, uric acid (UA), and total cholesterol (TC) between pSS-OA and pSS-nOA patients (P < 0.050). Logistic regression analysis showed that age (OR = 1.965; P = 0.009) and joint pain (OR = 3.382; P < 0.001) were dangerous factors associated with OA. Interestingly, although the level of UA, TC, and triglycerides (TG) was shown to be positive with OA, there was no statistical significance after the OR was computed in the four-cell table. In pSS-arthritis, EULAR Sjögren's syndrome disease activity index (ESSDAI) (P = 0.011), the frequency of joint pain (P < 0.001), and muscular involvement (P = 0.037) were higher than non-arthritis group. In pSS patients only presenting with joint pain, arthritis patients had higher ESSDAI and system involvements, but lower UA and TG levels compared with OA group (P < 0.050). CONCLUSION: In pSS patients with arthralgia, OA accounted for the majority. pSS patients with advanced age and more pronounced metabolic characteristics, such as elevated blood lipids and uric acid, was a key factor in groups at risk for OA. However, arthritis patients had higher rates of dry mouth and eye, higher disease activity, antibodies positive, and more organs damage. In the future, it may be necessary to be more cautious in the diagnosis of joint manifestations in pSS patients in order to make the appropriate treatments.

Predictors of poor prognosis in ANCA-associated vasculitis (AAV): a single-center prospective study of inpatients in China.

To identify potential predictors by assessing adverse outcomes in ANCA-associated vasculitis (AAV) patients. Eighty-nine untreated AAV patients were followed up to January 31, 2022, death, or loss of follow-up. Clinical characteristics, laboratory tests, treatment, and progress were collected, and disease activity was evaluated via Birmingham Vasculitis Activity Score (BVAS). We determined risk factors of high-risk events, defined as developing tumors, renal replacement therapy (RRT), and death. Patients and renal survivals were computed by the Kaplan-Meier curve analysis. Cox regression analysis was performed for assessing variables for predicting death. During 267 person-years follow-up, 46 patients occurred high-risk events, including 20 patients receiving RRT, 12 patients developing tumors, and 29 patients who died mostly from organ failure and infection. Decreased estimated glomerular filtration rate (eGFR) (P < 0.001) and complement 3 levels (P = 0.019) were associated with high-risk events. Patients with lower serum potassium tended to develop tumors (P = 0.033); with higher BVAS (HR = 1.290, 95%CI 1.075-1.549, P = 0.006) and lower eGFR (HR = 0.782, 95%CI 0.680-0.901, P = 0.001) were more likely to undergo RRT. Patients with cardio and renal involvement exhibited a lower frequency of renal survival and all-cause mortality. Through multivariate COX analysis, age (HR = 1.016, 95%CI 1.016-1.105, P = 0.006) and eGFR (HR = 0.982, 95%CI 0.968-0.997, P = 0.018) predicted death in AAV, separately. The BVAS and eGFR could be a great prognosticator for RRT, while age and eGFR can independently predict the death. Serum potassium level and immunoglobulins should be focused on their predictor value in development of cancer and renal outcomes in AAV patients.

Effects of Laser Machining Aluminum Alloy in Different Media.

To study the effects of aluminum alloys processed by a laser in air and water and at different water velocities, corresponding experiments were conducted and the impacting effects of different water velocities on the surface of the workpiece were simulated, respectively. The results show that when laser processing aluminum alloy materials in air, there is more slag and a recondensation layer on both sides of the groove, the heat-affected zone is larger and the surface processing quality is poor. When laser processing aluminum alloy materials in water, the processing quality is improved. With the increase in water velocity, the impacting and cooling effect is enhanced, the groove depth and groove width show a trend of first increasing and then decreasing, the slag and recondensation layer on both sides of the groove are reduced, the heat-affected zone is reduced and the processing quality of the groove is improved. When the water velocity reaches 30 m/s, a better groove can be obtained. Laser processing aluminum alloy materials in water can obtain better processing quality than laser processing in air.

Paraquat-induced oxidative stress regulates N6-methyladenosine (m6A) modification of long noncoding RNAs in Neuro-2a cells.

Paraquat (PQ) is a ubiquitously applied herbicide. Long-term PQ exposure with low dose has been reported to induce abnormal expression of long non-coding RNAs (lncRNAs) in brain nerve cells, which could further lead to Parkinson's disease (PD). N6-methyladenosine (m6A) modification has recently been identified as having an important role in regulating the function of lncRNAs. However, how m6A modification regulates lncRNAs following PQ exposure remains largely unknown. Herein, this study reported m6A modification of lncRNAs in mouse neuroblastoma cells (Neuro-2a) following PQ induced reactive oxide species (ROS). M6A sequencing was performed to explore the m6A modificated pattern of lncRNAs in Neuro-2a cells which were treated with 200 µM PQ for 3 h. It was found that PQ hypermethylated total RNA and changed the expression of m6A methyltransferase and demethylase proteins, which leading to the alteration of m6A modification of lncRNAs. Furthermore, the functional analysis further revealed that N-acetyl-L-cysteine (NAC)，a ROS scavengers, partly reversed PQ-induced distinct m6A modificated pattern of lncRNAs. In addition, tow specific m6A modified lncRNAs were identified: cell division cycle 5-like (lncRNA CDC5L) and signal transducer and activator of transcription 3 (lncRNA STAT3), which could influence downstream autophagy related biological function. In summary, this work could potentially contribute to the new insight of lncRNAs m6A modification mechanism in the field of environmental toxicology.

Relapsing Polychondritis Associated with Miscellaneous Ocular Symptoms and Increased IgA: a Case Report.

A male patient had suffered miscellaneous ocular symptoms for 20 years with auricular dysmorphosis and was diagnosed with Relapsing Polychondritis (RP) in the ear, nose, joints, and costal cartilage. The patient lost his vision owing to recurrent ocular symptoms for decades. He presented an increased IgA and was diagnosed with monoclonal gammopathy of undetermined significance (MGUS) and treated by prednisone and cyclophosphamide. His ocular symptoms relieved and serum IgA decreased after six months. In conclusion, RP is a systemic disease with a wide range of clinical symptoms and may lead to serious complications.

Effects of individualized administration of folic acid on prothrombotic state and vascular endothelial function with H-type hypertension: A double-blinded, randomized clinical cohort study.

BACKGROUND: Hypertension and hyperhomocysteinemia (HHcy) have long been associated with adverse cardiovascular and cerebrovascular health outcomes. This study evaluated the effect of individualized administration of folic acid (FA) on homocysteine (Hcy) levels, prothrombotic state, and blood pressure (BP) in patients with H-type hypertension (combination of HHcy and hypertension). METHODS: In this double-blinded, randomized clinical cohort study, 126 patients with H-type hypertension who were treated at our hospital were randomly divided into treatment and control groups (n = 55 each). The control group was treated with oral levamlodipine besylate tablets 2.5 mg and placebo, once a day (in the morning). The treatment group was first treated with oral levamlodipine besylate 2.5 mg and FA tablets 0.8 mg, once a day (in the morning), for 12 weeks. Then, in a second 12-week phase, the FA dose was adjusted using the methylene tetrahydrofolate reductase C677 polymorphism genotype. The levels of Hcy and coagulation factors, prothrombotic state parameters, BP, and adverse drug reactions were compared between the 2 groups. RESULTS: Pretreatment general patient characteristics, including Hcy levels, were similar between the 2 groups (P > .05). BP and prothrombotic status did not differ before and after the first phase of treatment (P > .05). However, Hcy and endothelin-1 (ET-1) levels decreased, while nitric oxide levels increased significantly in the intervention group (P < .05). In the second phase, after 3 months' treatment with an FA dose adjusted according to methylene tetrahydrofolate reductase C677T genotype, the Hcy and ET-1/NO levels were significantly decreased in the intervention group and were lower than those after the first treatment phase and lower than in the control group (P < .01). BP, D-dimer levels, and fibrinogen scores were significantly lower after the second treatment phase (P < .01). There was no significant difference in the incidence of adverse drug reactions between the 2 groups (P > .05). CONCLUSIONS: Individualized administration of FA tablets can effectively reduce BP, and Hcy and coagulation factor levels, and significantly improve prothrombotic status in patients with H-type hypertension.

N6-methyladenosine(m6A) demethylase FTO regulates cellular apoptosis following cobalt-induced oxidative stress.

Cobalt is an environmental toxicant that is known to damage human health. However, the molecular mechanisms underlying cobalt-induced neurotoxicity have not been elucidated in detail. In the present research, we used human neuroglioma H4 cells as an in vitro model. Cells were exposed to CoCl2 (0, 100, 200, 400 µM) for 24 h. We performed m6A sequencing techniques and constructed FTO-knockdown/FTO-overexpressing cells to investigate the role of FTO-mediated m6A modification in regulating apoptosis following CoCl2 induced oxidative stress. Our study has shown CoCl2 exposure led to the decrease of demethylase FTO as well as elevated oxidative stress. However, NAC treatment could partly reverse the reduction of FTO expression as well as the degree of ROS via eliminating oxidative stress. Meanwhile, MeRIP-seq and RNA-seq further revealed the potential function m6A modification in regulating apoptosis. More importantly, KEGG pathway and Gene ontology (GO) analyses further elucidated that the differentially m6A-modified genes were aggregated in apoptosis-related pathways. Mechanistic analysis indicated that knockdown of FTO facilitated CoCl2-induced apoptosis via caspase activation and G1/S cell cycle arrest. Nevertheless, overexpression of FTO partly attenuated the increased apoptosis following CoCl2 exposure. More notably, we observed that FTO regulated apoptosis in an m6A-dependent manner. Therefore, our findings reveal that CoCl2 induced ROS affected the m6A modification of apoptosis-related genes by decreasing the expression of FTO, thereby resulting in the activation of apoptosis. These findings provide important insights into CoCl2-induced apoptosis and m6A modification and propose a novel strategy for studying environmental toxicant-related neurodegeneration.

The Efficiency of Hydroxychloroquine for the Treatment of Primary Sjögren's Syndrome: A Systematic Review and Meta-Analysis.

Objectives: This meta-analysis was conducted to evaluate the effects of hydroxychloroquine (HCQ) in the treatment of primary Sjögren's syndrome (pSS). Methods: Nine databases were searched for data collection. We used clinical features, including involvement in superficial tissues and visceral systems, and experimental findings, including Schirmer's test, unstimulated salivary flow rate (uSFR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and immunoglobulins (IgG, IgM and IgA) as major outcome measures. The Downs and Black quality assessment tool and RevMan 5.3 were used to assess the methodological quality and statistical analysis, respectively. Results: Thirteen studies with pSS patients, consisting of two randomized controlled studies, four retrospective studies and seven prospective studies were analyzed. Results showed that HCQ treatment significantly improved the oral symptoms of pSS patients compared to non-HCQ treatment (P = 0.003). Similar trends favoring HCQ treatment were observed for uSFR (p = 0.05), CRP (p = 0.0008), ESR (p < 0.00001), IgM (p = 0.007) and IgA (p = 0.05). However, no significant improvement was observed in other clinical features, including ocular involvement, fatigue, articular lesions, pulmonary, neurological and lymphoproliferative symptoms, renal organs and other experimental parameters in the HCQ treatment group compared to the non-HCQ treatment group. Conclusion: HCQ treatment showed moderate efficacy to improve oral symptoms, uSFR, ESR, CRP, IgM and IgA. However, HCQ could not alleviate organ-specific systemic involvement. Systematic Review Registration:We have registered on the PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], and the registration number is identifier [CRD42020205624].

Paraquat-induced oxidative stress regulates N6-methyladenosine (m6A) modification of circular RNAs.

Paraquat (PQ), a widely used herbicide and well-known oxidative stress inducer, has been linked to numerous neurodegenerative diseases, but the underlying mechanism(s) remains unknown. Circular RNAs (circRNAs) have recently been reported to be associated with oxidative stress in Parkinson's disease. Herein, we performed methylated RNA immunoprecipitation and RNA sequencing assays for mouse neuroblastoma (Neuro-2a) cells and successfully established a positive link between the alteration of circRNAs driven by m6A modification and PQ-induced oxidative stress. We observed oxidative stress and antioxidative stress present distinct m6A modification pattern of circRNAs as well as biological effect. Gene ontology and pathway analysis predicted that differentially m6A-methylated and expressed circRNAs are highly clustered in pathways associated with function and development of nervous system, including axon cargo transport, nervous system development, long-term potentiation, and neurotrophic signaling pathways. Moreover, we demonstrated that the alteration of m6A-methylated circRNAs upon PQ exposure could be partially reversed by N-acetylcysteine pretreatment. The mechanistic analysis further demonstrated that N-acetylcysteine pretreatment attenuated the decreased expression of target genes (UBC and PPP2CA) induced by PQ. These findings revealed distinct patterns of differentially m6A-modified circRNAs, indicating that m6A could participate in a specific regulatory network of circRNAs to modulate the expression of downstream genes in response to PQ-induced oxidative stress. In conclusion, our work established a link between m6A modification of circRNAs and PQ-induced oxidative stress, and further studies are required to explore the underlying molecular mechanisms associated with PQ-induced neurotoxicity.

Comparison of iguratimod and conventional cyclophosphamide with sequential azathioprine as treatment of active lupus nephritis: study protocol for a multi-center, randomized, controlled clinical trial (iGeLU study).

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up. METHODS/DESIGN: This study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test. DISCUSSION: Most patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20-35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02936375 . Registered on October 18, 2016.

High-Performance Ultrafine Bubble Aeration on Janus Aluminum Foil Prepared by Laser Microfabrication.

Aeration is a mass transfer process, in which gas is dispersed into a liquid by utilizing air inflation or agitation. Typically, a microporous device is often used for aeration. Increasing the gas flow rate and decreasing the pore size reduce the bubble size, but the surface wettability of the gas/solid interface also has a significant impact on the bubble size, which is rarely studied. In this study, a superhydrophilic/superhydrophobic Janus aluminum foil (JAF) is fabricated by laser microstructuring and low surface energy modification. The gas-repelling superhydrophilic surface not only facilitates ultrafine bubble generation but also allows the bubbles to detach from the aerator surface quickly, while the superhydrophobic surface prevents water from infiltrating into the aeration chamber and reduces the mass transfer resistance. The micropores with different diameters are obtained by adjusting the laser processing parameters. The pore prepared by the laser is uniform, consequently leading to the uniform bubble size. When the pore diameter is set to 30 µm, the diameter of bubbles released from the superhydrophilic surface of the JAF is only 0.326 mm, and the gas dissolution rate is about six times that of the double-sided superhydrophobic aluminum foil. This simple, low-cost, and controllable method of the laser processing JAF has broad applications in wastewater treatment, energy production, and aquaculture.

[Recurrent vulvar rashes in a girl aged 22 months for more than half a year].

A girl, aged 22 months, attended the hospital due to recurrent vulvar rashes for more than half a year. Skin biopsy showed Langerhans cell histiocytosis, and evaluation of systemic conditions showed no systemic involvement. Therefore, the girl was diagnosed with Langerhans cell histiocytosis (skin type). In conclusion, for rashes on the vulva alone, if there are no specific clinical manifestations, the possibility of Langerhans cell histiocytosis should be considered after molluscum contagiosum, sexually transmitted diseases, and Fordyce disease are excluded.

The negative role of histone acetylation in cobalt chloride-induced neurodegenerative damages in SHSY5Y cells.

Cobalt has been known for its neurotoxicity in numerous studies. However, the molecular mechanism underlying cobalt-induced neurotoxicity remains largely unknown. In this study, two neuroblastoma (SHSY5Y and N2a) cell lines and a phaeochromocytoma (PC12) line were used as in vitro models. Cells were treated for 24 h with 50, 100, 200, 300, 400 µM cobalt chloride (CoCl2) or cultured with 300 µM CoCl2 for 4, 8, 12 and 24 h to investigate the effects of histone acetylation on CoCl2-induced neurodegenerative damages. Our findings demonstrate that CoCl2 suppresses the acetylation of histone H3 and H4 in a time-dependent and dosage-dependent manner. Furthermore, CoCl2 selectively decreases the expression and activity of histone acetyltransferase (HAT) but has no effects on histone deacetylase (HDAC) in SHSY5Y cells. More importantly, we show that 100 ng/mL HDAC inhibitor trichostatin (TSA) pre-treatment partly attenuates 300 µM CoCl2-induced neurodegenerative damages in SHSY5Y cells. Mechanistic analyses show that CoCl2-induced neurodegenerative damages are associated with the dysfunction of APP, BACE1, PSEN1, NEP and HIF-1α genes, whose expression are partly mediated by histone modification. In summary, we demonstrate that histone acetylation is involved in CoCl2-induced neurodegenerative damages. Our study indicates an important connection between histone modification and the pathological process of neurodegenerative damages and provides a mechanism for cobalt-mediated epigenetic regulation.

Mesenchymal stem cells negatively regulate CD4+ T cell activation in patients with primary Sjögren syndrome through the miRNA­125b and miRNA­155 TCR pathway.

Treatment with mesenchymal stem cells (MSCs) has been revealed to suppress CD4+ T cells and autoimmunity in both mouse models and patients with primary Sjögren syndrome (pSS); however, the underlying mechanism remains unclear. MicroRNAs (miRNAs or miRs) mediate CD4+ T cell activation, but the mechanism is not understood, particularly for CD4+ T cells treated with MSCs. Characterization of miRNAs may reveal pSS pathogenesis, guide MSC treatment and provide more personalized management options. The present study aimed to perform an miRNome analysis of quiescent and T cell receptor (TCR)­activated CD4+ T cells treated with MSCs via miRNA profiles and bioinformatics. Following 72 h of co­culture, MSCs inhibited TCR­induced CD4+ T cell activation and decreased IFN­Î³ levels. The numbers of aberrant miRNAs in pSS naïve (vs. healthy naïve), pSS activation (vs. pSS naïve), MSC treatment and pre­IFN­Î³ MSC treatment (vs. pSS activation) groups were 42, 55, 27 and 32, respectively. Gene enrichment analysis revealed that 259 pathways were associated with CD4+ T cell stimulation, and 240 pathways were associated with MSC treatment. Increased miRNA­7150 and miRNA­5096 and decreased miRNA­125b­5p and miRNA­22­3p levels in activated CD4+ T cells from patients with pSS were reversed by MSC treatment. Notably, the proliferation of CD4+ T cells and CD4+ IFN­Î³+ cells, expression levels of miRNA­125b­5p and miRNA­155 in CD4+ T cells and supernatant IFN­Î³ secretion were associated with disease activity. miRNA may play a vital role in MSC treatment for activated CD4+ T cells. The results indicated that the expression levels of miRNA­125b­5p and miRNA­155 in TCR­activated CD4+ T cells from patients with pSS may provide insight regarding autoimmune diseases and offer a novel target for prospective treatment. Therefore, these results may be crucial in providing MSC treatment for pSS.