circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

The CsTM alters multicellular trichome morphology and enhances resistance against aphid by interacting with CsTIP1;1 in cucumber.

The multicellular trichomes of cucumber (Cucumis sativus L.) serve as the primary defense barrier against external factors, whose impact extends beyond plant growth and development to include commercial characteristics of fruits. The aphid (Aphis gossypii Glover) is one of prominent pests in cucumber cultivation. However, the relationship between physical properties of trichomes and the aphid resistance at molecular level remains largely unexplored. Here, a spontaneous mutant trichome morphology (tm) was characterized by increased susceptibility towards aphid. Further observations showed the tm exhibited a higher and narrower trichome base, which was significantly distinguishable from that in wild-type (WT). We conducted map-based cloning and identified the candidate, CsTM, encoding a C-lectin receptor-like kinase. The knockout mutant demonstrated the role of CsTM in trichome morphogenesis. The presence of SNP does not regulate the relative expression of CsTM, but diminishes the CsTM abundance of membrane proteins in tm. Interestingly, CsTM was found to interact with CsTIP1;1, which encodes an aquaporin with extensive reports in plant resistance and growth development. The subsequent aphid resistance experiments revealed that both CsTM and CsTIP1;1 regulated the development of trichomes and conferred resistance against aphid by affecting cytoplasmic H2O2 contents. Transcriptome analysis revealed a significant enrichment of genes associated with pathogenesis, calcium binding and cellulose synthase. Overall, our study elucidates an unidentified mechanism that CsTM-CsTIP1;1 alters multicellular trichome morphology and enhances resistance against aphid, thus providing a wholly new perspective for trichome morphogenesis in cucumber.

Overcoming low initial coulombic efficiencies of Si anodes through prelithiation in all-solid-state batteries.

All-solid-state batteries using Si as the anode have shown promising performance without continual solid-electrolyte interface (SEI) growth. However, the first cycle irreversible capacity loss yields low initial Coulombic efficiency (ICE) of Si, limiting the energy density. To address this, we adopt a prelithiation strategy to increase ICE and conductivity of all-solid-state Si cells. A significant increase in ICE is observed for Li1Si anode paired with a lithium cobalt oxide (LCO) cathode. Additionally, a comparison with lithium nickel manganese cobalt oxide (NCM) reveals that performance improvements with Si prelithiation is only applicable for full cells dominated by high anode irreversibility. With this prelithiation strategy, 15% improvement in capacity retention is achieved after 1000 cycles compared to a pure Si. With Li1Si, a high areal capacity of up to 10 mAh cm-2 is attained using a dry-processed LCO cathode film, suggesting that the prelithiation method may be suitable for high-loading next-generation all-solid-state batteries.

Phase-Dependent Magnetic Proximity Modulations on Valley Polarization and Splitting.

Proximate-induced magnetic interactions present a promising strategy for precise manipulation of valley degrees of freedom. Taking advantage of the splendid valleytronic platform of transition metal dichalcogenides, magnetic two-dimensional VSe2 with different phases are introduced to intervene in the spin of electrons and modulate their valleytronic properties. When constructing the heterostructures, 1T-VSe2/WX2 (X = S and Se) showcases significant improvement in the valley polarizations at room temperature, while 2H-VSe2/WX2 exhibits superior performance at low temperatures and demonstrates heightened sensitivity to the external magnetic field. Simultaneously, considerable valley splitting with a large geff factor up to -29.0 is observed in 2H-VSe2/WS2, while it is negligible in 1T-VSe2/WX2. First-principles calculations reveal a phase-dependent magnetic proximity mechanism on the valleytronic modulations, which is dominated by interfacial charge transfer in 1T-VSe2/WX2 and the proximity exchange field in 2H-VSe2/WX2 heterostructures. The effective control over valley degrees of freedom will bridge the valleytronic physics and devices, rendering enormous potential in the field of valley quantum applications.

Increased interleukin-9 and Th9 cells in patients with refractory Graves' disease and interleukin-9 polymorphisms are associated with autoimmune thyroid diseases.

Introduction: Autoimmune thyroid diseases (AITDs) are prevalent disorders, primarily encompassing Graves' disease (GD) and Hashimoto's thyroiditis (HT). Despite their common occurrence, the etiology of AITDs remains elusive. Th9 cells, a new subset of CD4+T cells with immunomodulatory properties, have been linked to the development of various autoimmune diseases. However, research on the role of Th9 cells in AITDs is limited. Methods: We investigated the expression of Th9 cells,their functional cytokine IL-9, and transcription factor IRF4 in peripheral blood mononuclear cells (PBMCs) and plasma of AITD patients and healthy controls. Additionally, we explored the genetic association between four loci polymorphisms (rs31564, rs2069879, rs1859430, and rs2069868) of the IL-9 gene and AITDs. Results: We reported, for the first time, that refractory GD patients exhibited elevated mRNA levels of IL-9 and IRF4 in PBMCs, increased IL-9 protein levels in plasma, and a higher proportion of Th9 cells in peripheral blood when compared to normal controls. Furthermore, human recombinant IL-9 protein was found to enhance IFN-g secretion in PBMCs from both GD patients and normal controls. At the genetic association level, after adjusting for age and sex, the rs2069879 polymorphism exhibited a significant association with AITDs under an additive model (P<0.001, OR= 0.05, 95% CI=0.03-0.08). Discussion: Our results reveal that Th9 cells may exert a pivotal role in the pathogenesis and progression of refractory GD and HT, and IL-9 holds promise as a novel therapeutic target for the management of AITDs.

Disproportional signal of pericarditis with biological diseasemodifying antirheumatic drugs (bDMARDs) in patients with ankylosing spondylitis: a disproportionality analysis in the FAERS database.

Objective: This study aimed to investigate the potential association between biological disease-modifying antirheumatic drugs (bDMARDs) and pericarditis and uncover relevant clinical characteristics in ankylosing spondylitis (AS). Methods: Reports of pericarditis recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004-December 2022) were identified through the preferred term "pericarditis." Demographic and clinical characteristics were described, and disproportionality signals were assessed through the reporting odds ratio (ROR) and information component (IC). A significant signal was detected if the lower bound of IC (IC025) was more than zero. Results: We found 1,874 reports of pericarditis with bDMARDs (11.3% of cases with fatal outcomes). Adalimumab (IC025 3.24), infliximab (IC025 4.90), golimumab (IC025 5.40), certolizumab (IC025 5.43), etanercept (IC025 3.24), secukinumab (IC025 3.97), and ustekinumab (IC025 7.61) exhibit significant disproportionality signals compared to other medications in the FAERS database. After excluding pre-existing diseases and co-treated drugs that may increase the susceptibility of pericarditis, the disproportionality signal associated with infliximab, certolizumab, etanercept, secukinumab, and ustekinumab remained strong. Pericarditis cases associated with all bDMARDs were predominantly recorded in women aged 25-65 years. Conclusion: More reports of pericarditis were detected with AS patients on bDMARDs than with other drugs in the overall database. Further studies are warranted to investigate the underlying mechanisms and identify patient-related susceptibility factors, thus supporting timely diagnosis and safe(r) prescribing of bDMARDs.

Global fungal-host interactome mapping identifies host targets of candidalysin.

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

Effects of altitude on thyroid disorders according to Chinese three-rung, ladder-like topography: national cross-sectional study.

BACKGROUND: Chinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015-2017 that covered all 31 mainland Chinese provinces. METHODS: A total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000-500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500-100 m) and B (< 100 m). Associations between geographic factors and thyroid disorders were assessed using linear and binary logistic regression analyses. RESULTS: Participants in the first ladder group were associated with lower thyroid peroxidase (ß = -4.69; P = 0.00), thyroglobulin antibody levels (ß = -11.08; P = 0.01), and the largest thyroid volume (ß = 1.74; P = 0.00), compared with the other groups. The second ladder group was associated with autoimmune thyroiditis (odds ratio = 1.30, 95% confidence interval [1.18-1.43]) and subclinical hypothyroidism (odds ratio = 0.61, 95%confidence interval [0.57-0.66]) (P < 0.05) compared with the first ladder group. Group A (third ladder) (500-100 m) was associated with thyroid nodules and subclinical hypothyroidism (P < 0.05). Furthermore, group B (< 100 m) was positively associated with autoimmune thyroiditis, thyroid peroxidase and thyroglobulin antibody positivity, and negatively associated with overt hypothyroidism, subclinical hypothyroidism, and goiter compared with the first ladder group(P < 0.05). CONCLUSION: We are the first to investigate the association between different ladder regions and thyroid disorders according to unique Chinese topographic features. The prevalence of thyroid disorders varied among the three-rung ladder-like topography groups in China, with the exception of overt hyperthyroidism.

Use of autologous iliac crest graft and free anterolateral femoral skin flap in diabetic foot ulcers: a case report.

BACKGROUND: Diabetic foot has a great impact on the life of patients. Its treatment involves a multi-disciplinary and multi-direction approach, which requires not only soft tissue repair, but also bone reconstruction and functional repair. CASE PRESENTATION: A 51-year-old Chinese man with a three-year history of diabetes was diagnosed with ulcers in his left foot. We performed a successful procedure, and the different strategies we adopted helped to avoid serious complications during treatment. The patient was treated with debridement, bone cement, iliac crest graft, and anterolateral femoral skin flap, and recovered well. CONCLUSION: There is a dearth of reports pertaining to treatment of diabetic foot in patients with midfoot bone and soft tissue loss. In this report, we present an effective method that we used to reconstruct the loss of midfoot in a patient with diabetic foot, illustrating a successful therapeutic strategy for saving limbs in this complex medical condition.

Ten-year follow-up investigation of stroke risk in systemic lupus erythematosus.

BACKGROUND AND PURPOSE: To analyse the long-term risk of ischaemic stroke and the clinical effects of antithrombotics on the risk of haemorrhagic stroke in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective cohort study was conducted using a population-based database taken from Taiwan National Health Insurance Research Database. Patients with SLE between 2000 and 2008 were registered and matched with two controls by the index date, age, gender and Charlson Comorbidity Index (CCI). These subjects were followed until either stroke event or 31 December 2013. Adjusted HRs (aHRs) for strokes were estimated with Cox regression models, and the cumulative incidence of ischaemic stroke was analysed by log-rank test and Kaplan-Meier survival analysis. RESULTS: In total, 8310 patients with SLE and 16 620 patients without SLE were included. In general, patients with SLE had higher rates of ischaemic stroke (5.4% vs 3.3%) and haemorrhagic stroke (1.5% vs 0.6%) than in controls. In multivariate analysis adjusted to age, gender, CCI, urbanisation level and antithrombotics uses, aHRs of all strokes, ischaemic stroke and haemorrhagic stroke were 1.73 (95% CI: 1.54 to 1.94), 1.65 (95% CI: 1.45 to 1.87) and 2.24 (95% CI: 1.71 to 2.95), respectively, in patients with SLE. Patients with SLE were significantly more likely to suffer ischaemic stroke than patients without SLE, even 10 years after SLE diagnosis (6.12% vs 3.50%, p<0.001). Antiplatelet use increased the risk of haemorrhagic stroke in SLE group (aHR=1.74, 95% CI: 1.18 to 2.57). CONCLUSIONS: Patients with SLE are at greater risk of developing ischaemic stroke that lasts for 10 years. Antiplatelets should be carefully administered to prevent cardiovascular events in patients with SLE due to the risk of haemorrhagic stroke.

Dual antiplatelet therapy is associated with favorable outcome in acute minor stroke with an onset-to-door time beyond 24 h.

BACKGROUND/PURPOSE: In patients with noncardioembolic acute minor ischemic stroke (AMIS), dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 24 h after stroke onset was more effective than aspirin alone. This study investigated the efficacy and safety of DAPT in AMIS patients with an onset-to-door time (OTDT) of more than 24 h. METHODS: This was a retrospective analysis of a prospective stroke registry from 2015 to 2021. Patients with AMIS and an OTDT within seven days were classified into the Early (≤24 h) and Late groups (>24 h) according to the time of antiplatelet administration after stroke onset. RESULTS: In total, 691 patients were identified. Of these, 446 (64.5%) and 245 (35.5%) patients were classified into the Early and Late groups, respectively. The rates of recurrent infarction and symptomatic intracranial hemorrhage at 90 days were similar between the single antiplatelet therapy (SAPT) and DAPT subgroups in both the Early and Late groups. More patients in the DAPT subgroup had a favorable outcome (modified Rankin scale of 0-1) at 90 days in both Early (84.2% versus 75.0%, p = 0.016) and Late (88.2% versus 76.9%, p = 0.040) groups. DAPT was independently associated with a favorable outcome in both the Early (odds ratio, 1.95; 95% CI, 1.15-3.32; p = 0.013) and Late (odds ratio, 2.72; 95% CI, 1.14-6.48; p = 0.024) groups. CONCLUSION: In patients with AMIS and an OTDT of more than 24 h, DAPT was associated with a favorable outcome at 90 days.

Chaepseubakerins A-J, ten undescribed cytotoxic [11]-chaetoglobosins from an endophytic fungus Pseudeurotium bakeri.

Ten previously unreported [11]-chaetoglobosins, chaepseubakerins A-J (1-10), were characterized from the solid rice-based culture of Pseudeurotium bakeri P1-1-1, an endophyte harbored in the roots of Macrocoma tenue subsp. sullivantii Vitt. (Orthotrichaceae). Their structures were determined by spectroscopic analysis, single-crystal X-ray diffraction (Cu Kα radiation), and chemical methods. Chaepseubakerin A (1) exhibited significant cytotoxic effects against seven human cancer cell lines, A549, A427, HCT116, HT-29, HeLa, HepG2, and MCF-7, with IC50 values of 2.9, 3.0, 4.0, 4.4, 7.1, 6.7, and 8.9 µM, respectively. Mechanistically, 1 induced G2/M cell cycle arrest and apoptosis in A549, Hela, and HCT116 cells in a dose dependent manner.

Use of dipeptidyl peptidase-4 inhibitors was associated with a lower risk of Parkinson's disease in diabetic patients.

Diabetes mellitus is a risk factor for Parkinson's disease (PD). While animal studies have supported the benefits of incretin-based therapies, including dipeptidyl peptidase-4 (DPP4) inhibitors, in PD, clinical research has yielded controversial results. This cohort study aimed to assess the relationship between PD incidence and the utilization of DPP4 inhibitor in diabetic patients. Using Taiwan's National Health Insurance Research Database from 2009 to 2018, diabetic patients receiving metformin plus at least one second-line oral antidiabetic (OAD) were enrolled. The patients were categorized as DPP4 inhibitor users and non-users. Propensity score matching was employed to establish a 1:1 ratio between DPP4 inhibitor users and non-users. Among the 205,910 patients enrolled, 149 were diagnosed with PD during follow-up. The incidence rate was 0.29 per 1000 person-years for DPP4 inhibitor users and 0.55 per 1000 person-years for the non-users. DPP4 inhibitor users exhibited a significantly lower risk of PD (adjusted hazard ratio, 0.51; 95% CI 0.39-0.68). Among DPP4 inhibitor users, vildagliptin showed the strongest correlation with a reduction in the risk of PD. This study demonstrates that the use of DPP4 inhibitors along with metformin in diabetic patients is associated with a lower risk of PD compared to those using other OADs.

Maggot debridement therapy stimulates wound healing by altering macrophage activation.

The purpose of this study is to determine the impact of maggot debridement therapy (MDT) on macrophages during the healing process of diabetic foot ulcers (DFU). The activation phenotype of macrophages during wound healing following MDT was evaluated using double staining immunohistochemistry (IHC). In addition, markers associated with macrophage activation were discovered using immunoblotting and real-time polymerase chain reaction (PCR). During the process of diabetic wound healing following MDT, the presence and over-expression of M2 macrophages were observed, while the under-expression of M1 macrophages was noted. In addition, the activation markers of macrophages exhibited a correlation with the indicated Th1/Th2 cytokines. MDT interventions have the potential to modulate macrophage activity, thereby aiding in the healing of diabetic foot wounds.

The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells.

Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1ß-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells. This is mediated by IL-1ß secretion via ß-glucan/Dectin-1/CARD9 pathway. Analysis of human samples confirms that enriched A. sydowii is associated with immunosuppression and poor patient outcome. Our findings suggest that intratumor mycobiome, albeit at low biomass, promotes lung cancer progression and could be targeted at the strain level to improve patients with LUAD outcome.

Poly(butylene adipate-co-terephthalate) biodegradation by Purpureocillium lilacinum strain BA1S.

Poly(butylene adipate-co-terephthalate) (PBAT), a promising biodegradable aliphatic-aromatic copolyester material, can be applied as an alternative material to reduce the adverse effects of conventional plastics. However, the degradation of PBAT plastics in soil is time-consuming, and effective PBAT-degrading microorganisms have rarely been reported. In this study, the biodegradation properties of PBAT by an elite fungal strain and related mechanisms were elucidated. Four PBAT-degrading fungal strains were isolated from farmland soils, and Purpureocillium lilacinum strain BA1S showed a prominent degradation rate. It decomposed approximately 15 wt.% of the PBAT films 30 days after inoculation. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and Liquid chromatography mass spectrometry (LC‒MS) were conducted to analyze the physicochemical properties and composition of the byproducts after biodegradation. In the presence of PBAT, the lipolytic enzyme activities of BA1S were remarkably induced, and its cutinase gene was also significantly upregulated. Of note, the utilization of PBAT in BA1S cells was closely correlated with intracellular cytochrome P450 (CYP) monooxygenase. Furthermore, CreA-mediated carbon catabolite repression was confirmed to be involved in regulating PBAT-degrading hydrolases and affected the degradation efficiency. This study provides new insight into the degradation of PBAT by elite fungal strains and increases knowledge on the mechanism, which can be applied to control the biodegradability of PBAT films in the future. KEY POINTS: • Purpureocillium lilacinum strain BA1S was isolated from farmland soils and degraded PBAT plastic films at a prominent rate. • The lipolytic enzyme activities of strain BA1S were induced during coculture with PBAT, and the cutinase gene was significantly upregulated during PBAT degradation. • CreA-mediated carbon catabolite repression of BA1S plays an essential role in regulating the expression of PBAT-degrading hydrolases.

Shared biomarkers of multi-tissue origin for primary Sjogren's syndrome and their importance in immune microenvironment alterations.

With the recent advancement in omics and molecular techniques, a wealth of new molecular biomarkers have become available for the diagnosis and classification of primary Sjögren's syndrome (pSS) patients. However, whether these biomarkers are universal is of great interest to us. In this study, we used various methods to obtain shared biomarkers derived from multiple tissue in pSS patients and to explore their relationship with immune microenvironment alterations. First we identified differentially expressed genes (DEGs) between pSS and healthy controls utilizing nine mRNA microarray datasets obtained from the Gene Expression Omnibus (GEO). Then, shared biomarkers were filtered out using robust rank aggregation (RRA), data integration analysis, weighted gene co-expression network analysis (WGCNA), and least absolute selection and shrinkage operator (LASSO) regression; their roles in pSS and association with changes in the immune microenvironment were also analyzed. In addition, these biomarkers were further confirmed with both the testing set and immunohistochemistry (IHC). As a result, ten biomarkers, i.e., EPSTI1, IFI44, IFIT1, IFIT2, IFIT3, MX1, OAS1, PARP9, SAMD9L and TRIM22, were identified. Receiver operating characteristic (ROC) curves showed that the ten genes could discriminate pSS from controls. Gene set enrichment analysis (GSEA) showed that the enrichment of immune-related gene sets was significant in pSS patients with high expression of either biomarker. Furthermore, the association between some immunocytes and these biomarkers was identified. In the two distinct molecular patterns of pSS patients based on the expressions of these biomarkers, the proportions of immunocytes were significantly different. Our study identified shared biomarkers of multi-tissue origin and revealed their relationship with altered immune microenvironment in pSS patients. These markers not only have diagnostic implications but also provide potential immunotherapeutic targets for the clinical treatment of pSS patients.

An advanced treatment process for 3-high wastewater discharged from crude oil storage tanks.

The wastewater discharged from crude oil storage tanks (WCOST) contains high concentrations of salt and metal iron ions, and high chemical oxygen demand (COD). It belongs to "3-high" wastewater, which is difficult for purification. In this study, WCOST treatments were comparatively investigated via an advanced pretreatment and the traditional coagulation-microfiltration (CMF) processes. After WCOST was purified through the conventional CMF process, fouling occurred in the microfiltration (MF) membrane, which is rather harmful to the following reverse osmosis (RO) membrane unit, and the effluent featured high COD and UV254 values. The analysis confirmed that the MF fouling was due to the oxidation of ferrous ions, and the high COD and UV254 values were mainly attributable to the organic compounds with small molecular sizes, including aromatic-like and fulvic-like compounds. After the pretreatment of the advanced process consisting of aeration, manganese sand filtration, and activated carbon adsorption in combination with CMF process, the removal efficiencies of organic matter and total iron ions reached 97.3% and 99.8%, respectively. All the water indexes of the effluent, after treatment by the advanced multi-unit process, meet well the corresponding standard. The advanced pretreatment process reported herein displayed a great potential for alleviating the MF membrane fouling and enhanced the lifetime of the RO membrane system in the 3-high WCOST treatment.

Frequency and Treatment Regimens of Macular Edema in 1946 Consecutive Patients with Noninfectious Uveitis at a Tertiary Ophthalmic Center in Shaanxi, China.

INTRODUCTION: We investigated the frequency of uveitic macular edema (UME) in patients with different types of noninfectious uveitis and present the primary treatment methods for UME at a specialized eye center in Shaanxi Province, China. METHODS: We conducted a retrospective, noninterventional, observational survey involving 1946 patients with noninfectious uveitis (2816 eyes). The collected data included sex, age of uveitis onset, age of UME onset, anatomical classification of uveitis, and the treatment administered to UME patients. RESULTS: Of the 1946 patients with noninfectious uveitis, 929 (47.74%) were male and 1017 (52.26%) were female. The average age of all participants in the study was 42.19 ± 15.34 years, with average age at uveitis onset of 39.50 ± 15.52 years. Among the patients, 1003 (51.54%), 239 (12.28%), 410 (21.07%), and 294 (15.11%) had anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis, respectively. UME was observed in 134 (6.89%) of the uveitis patients. The average age of UME patients was 47.33 ± 17.17 years, with average age at uveitis onset of 45.78 ± 17.20 years. Out of the 134 UME patients, 3 (0.30%), 15 (6.28%), 47 (11.46%), and 69 (23.47%) had anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis, respectively. Among them, 37 were lost to follow-up, 44 received adalimumab (ADA) combined with low-dose prednisone and with or without conventional immunosuppressants, 19 received interferon-α2a therapy, 14 received intravitreal corticosteroid injections (such as dexamethasone implant or fluocinolone acetonide), 11 received low-dose corticosteroids combined with conventional immunosuppressants, 5 received only oral prednisone, and 4 received repeated peribulbar or subconjunctival injections of triamcinolone acetonide. CONCLUSIONS: At our tertiary ophthalmic center in Shaanxi Province, China, only 6.89% of patients with noninfectious uveitis were diagnosed with UME. The primary treatment modality for UME in our center is ADA, in accordance with treatment guidelines and the Chinese medical insurance reimbursement system.

Macular edema is a common complication that can cause vision loss in patients with uveitis. However, there is limited information about the occurrence of uveitic macular edema in the past two decades, and existing data mainly focus on developed countries such as the Netherlands and Italy. There are no relevant data for Asian countries such as China or Japan. In this study, we examined the frequency of uveitic macular edema in 1946 patients (2816 eyes) with different types of noninfectious uveitis who received treatment at a specialized eye center in Shaanxi Province, China, between January 2021 and October 2022. Among the uveitis patients, only 134 (6.89%) had uveitic macular edema. Out of these 134 patients, 3 (0.30%), 15 (6.28%), 47 (11.46%), and 69 (23.47%) had anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis, respectively. Additionally, we analyzed the treatment methods used for uveitic macular edema patients. In our center, the primary treatment approach for uveitic macular edema is adalimumab, in accordance with treatment guidelines and the Chinese medical insurance reimbursement system. Other treatment strategies include interferon-α2a therapy, intravitreal dexamethasone implants, and low-dose corticosteroids combined with conventional immunosuppressants. Our research provides valuable insights into the occurrence of uveitic macular edema in noninfectious uveitis patients and the current treatment practices at a single medical center in Shaanxi, China.