The novel peptide PEP-Z-2 potentially treats renal fibrosis in vivo and in vitro by regulating TGF-ß/Smad/AKT/MAPK signaling.

Renal fibrosis is a process in which excessive deposition of extracellular matrix leads to an increase in tissue hardness and gradual destruction of the renal parenchyma. Chronic kidney disease (CKD) commonly progresses to end-stage renal disease (ESRD), ultimately leading to renal failure. This disease has high incidence and mortality rates, but to date, effective treatment options are lacking. PEP-Z-2 is a collagen peptide isolated from redlip croaker scales and may have potential fibroprotective activity. In this study, PEP-Z-2 was found to alleviate unilateral ureteral obstruction (UUO)- and folic acid (FA)-induced kidney injury in a mouse model, reduce collagen deposition in tissues, normalize renal function, reduce the expression of fibrosis markers, reduce reactive oxygen species (ROS) production, and restore the balance of the oxidant/antioxidant system. In vitro experiments also demonstrated that PEP-Z-2 inhibits the TGF-ß-induced differentiation of fibroblasts and renal tubular epithelial cells into myofibroblasts and reduces the production of extracellular matrix (ECM) proteins such as fibronectin, Col I, and α-SMA, demonstrating notable therapeutic effects on renal fibrosis. This effect is achieved by regulating the TGF-ß/Smad/AKT/MAPK pathway. Our research suggested that PEP-Z-2 is a potential therapeutic drug for renal fibrosis, and peptides from aquatic organisms may constitute a new class of candidate drugs for the treatment of renal fibrosis and even other types of organ fibrosis.

Identification of RNMT as an immunotherapeutic and prognostic biomarker: From pan-cancer analysis to lung squamous cell carcinoma validation.

BACKGROUND: Dysregulation of RNA guanine-7 methyltransferase (RNMT) plays a crucial role in the tumor progression and immune responses. However, the detailed role of RNMT in pan-cancer is still unknown. METHODS: Bulk transcriptomic data of pan-cancer were obtained from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases. Single-cell transcriptomic and proteomics data of lung squamous cell carcinoma (LUSC) were analyzed in the Tumor Immune Single-cell Hub 2 (TISCH2) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, respectively. The correlation between RNMT expression and cancer prognosis was analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. The correlation of RNMT expression with common immunoregulators, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methyltransferase (DNMT) was analyzed. Additionally, the correlation between RNMT expression and immune infiltration level was evaluated. A total of 1287 machine learning combinations were used to construct prognostic models for LUSC. qRT-PCR and Western blot were used to validate the bioinformatics findings of RNMT upregulation in LUSC. RESULTS: RNMT was widely expressed across different cancers, with significant correlation to prognosis in cancers such as kidney chromophobe (KICH) (p = 0.0033, HR = 7.12), liver hepatocellular carcinoma (LIHC) (p = 0.01, HR = 1.41), and others. Notably, RNMT participates in the regulation of the tumor microenvironment. RNMT expression positively correlated with immune cell expression (Spearman's rank correlation, p < 0.05). Moreover, RNMT expression was strongly associated with immunoregulators, TMB, MSI, MMR, and DNMT in most cancer types. Notably, RNMT expression displayed excellent prognostic and immunological performance in LUSC. The expression of RNMT was mainly enriched in B cells of LUSC tissues. qRT-PCR and Western blot verified the high expression of RNMT in LUSC. CONCLUSION: RNMT expression widely correlated with prognosis and immune infiltration in various tumors, especially LUSC. The RNMT detection may provide a new idea for future tumor immune studies and treatment strategies.

The NRF2 activator RTA-408 ameliorates chronic alcohol exposure-induced cognitive impairment and NLRP3 inflammasome activation by modulating impaired mitophagy initiation.

BACKGROUND: Chronic alcohol exposure induces cognitive impairment and NLRP3 inflammasome activation in the mPFC (medial prefrontal cortex). Mitophagy plays a crucial role in neuroinflammation, and dysregulated mitophagy is associated with behavioral deficits. However, the potential relationships among mitophagy, inflammation, and cognitive impairment in the context of alcohol exposure have not yet been studied. NRF2 promotes the process of mitophagy, while alcohol inhibits NRF2 expression. Whether NRF2 activation can ameliorate defective mitophagy and neuroinflammation in the presence of alcohol remains unknown. METHODS: BV2 cells and primary microglia were treated with alcohol. C57BL/6J mice were repeatedly administered alcohol intragastrically. BNIP3-siRNA, PINK1-siRNA, CCCP and bafilomycin A1 were used to regulate mitophagy in BV2 cells. RTA-408 acted as an NRF2 activator. Mitochondrial dysfunction, mitophagy and NLRP3 inflammasome activation were assayed. Behavioral tests were used to assess cognition. RESULTS: Chronic alcohol exposure impaired the initiation of both receptor-mediated mitophagy and PINK1-mediated mitophagy in the mPFC and in vitro microglial cells. Silencing BNIP3 or PINK1 induced mitochondrial dysfunction and aggravated alcohol-induced NLRP3 inflammasome activation in BV2 cells. In addition, alcohol exposure inhibited the NRF2 expression both in vivo and in vitro. NRF2 activation by RTA-408 ameliorated NLRP3 inflammasome activation and mitophagy downregulation in microglia, ultimately improving cognitive impairment in the presence of alcohol. CONCLUSION: Chronic alcohol exposure-induced impaired mitophagy initiation contributed to NLRP3 inflammasome activation and cognitive deficits, which could be alleviated by NRF2 activation via RTA-408.

Aldo-keto reductase family 1 member A1 (AKR1A1) exerts a protective function in alcohol-associated liver disease by reducing 4-HNE accumulation and p53 activation.

BACKGROUND: The development of alcohol-associated liver disease (ALD) is influenced by the amount and duration of alcohol consumption. The resulting liver damage can range from reversible stages, such as steatosis, steatohepatitis and alcoholic fibrosis, to the advanced and irreversible stage of cirrhosis. Aldo-keto reductase family 1 member A1 (AKR1A1) is a member of the aldo-keto reductase family that catalyzes the reduction of aldehyde groups to their corresponding alcohols in an NADPH-dependent manner. AKR1A1 was found to be downregulated in patients diagnosed with ALD. This study aims to interpret the protective effects of AKR1A1 on the development of ALD. METHODS: A 5% alcohol-fed (AF) Akr1a1 knockout (Akr1a1-/-) mouse model and an AML12 hepatocyte model were used. The effects of AKR1A1 on liver function, inflammation, oxidative stress, lipid accumulation, and fibrosis were assessed by ELISA, western blotting, RT‒PCR, and a variety of histological staining methods in AF-induced wild-type (WT) and Akr1a1-/- mice compared to control liquid diet-fed (PF) WT and Akr1a1-/- mice. RESULTS: The results demonstrated that AF-WT mice expressed higher levels of AKR1A1 than WT mice fed a control diet, and they did not show any noticeable liver steatosis. However, AF-Akr1a1-/- mice displayed a lower survival rate and more severe liver injury than AF-WT mice, as demonstrated by increased proinflammatory cytokines, oxidative stress, lipid accumulation, fibrosis, and reduced antioxidant enzymes in their livers. Additionally, elevated levels of 4-HNE and p53 phosphorylation were observed in AF-Akr1a1-/- mice, suggesting that the loss of AKR1A1 led to increased 4-HNE accumulation and subsequent activation of p53, which contributed to the progression of ALD. Furthermore, in AML12 hepatocytes, Akr1a1 knockdown aggravated oxidative stress and steatosis induced by palmitic acid/oleic acid (P/O) inflammation induced by lipopolysaccharide (LPS), and fibrosis induced by TGF-ß1. CONCLUSIONS: This loss-of-function study suggests that AKR1A1 plays a liver-protective role during chronic alcohol consumption by reducing the accumulation of 4-HNE and inhibiting 4-HNE-mediated p53 activation.

Factors affecting the occurrence and accumulation of perfluoroalkyl acids in indoor dust in Tainan, Taiwan.

Perfluoroalkyl acids (PFAAs) are environmentally and biologically persistent chemicals. In this study, we investigated the concentrations of six PFAAs in dust samples collected from different indoor environments in a college campus in Tainan, Taiwan, and assessed the health risk of PFAAs exposure to college students. We also analyzed the effects of dust characteristics (total organic carbon, moisture content, and dust content) on PFAAs levels. With regard to the space type, the median of total PFAAs concentrations were in the order of laboratories (528.9 µg kg-1) > offices (304.2 µg kg-1) > dormitories (180.1 µg kg-1) > classrooms (105.1 µg kg-1). With regard to the height from the ground, the median total PFAAs concentrations were in the order of dust near the floors (>2 m; 383.6 µg kg-1) > near the ceiling (0-2 m; 202.5 µg kg-1) > on the ground (0 m; 145.6 µg kg-1). The main species of PFAAs, perfluorooctane sulfonate and short-chain perfluoroalkyl carboxylates, accounted for respectively 30%-60% and ∼20%-37% of total PFAAs pollution in the indoor space types and sampling heights under consideration. The average daily intake (ADI) values of six PFAAs for college students were found to be 0.059-0.126 ng kg-1 BW day-1 (BW: body weight), with dormitories and workplaces (i.e., laboratories and offices) accounting for over 40% and ∼50% of the ADI, respectively. The estimated hazard quotient ranged from 0.0029 to 0.0063, three orders of magnitude lower than 1, suggesting relatively low risks for college students exposed to the six PFAAs monitored in indoor dust. The analysis of dust characteristics revealed that total organic carbon did not have a significant effect on PFAAs levels as we expected. In contrast, dust moisture and cation content dominated PFAAs accumulation.

Trained immunity induced by high-salt diet impedes stroke recovery.

A high-salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity and mortality, remains unknown. Here, we report that HSD impairs long-term brain recovery after intracerebral hemorrhage, a severe form of stroke, despite salt withdrawal prior to the injury. Mechanistically, HSD induces innate immune priming and training in hematopoietic stem and progenitor cells (HSPCs) by downregulation of NR4a family and mitochondrial oxidative phosphorylation. This training compromises alternative activation of monocyte-derived macrophages (MDMs) without altering the initial inflammatory responses of the stroke brain. Healthy mice transplanted with bone marrow from HSD-fed mice retain signatures of reduced MDM reparative functions, further confirming a persistent form of innate immune memory that originates in the bone marrow. Loss of NR4a1 in macrophages recapitulates HSD-induced negative impacts on stroke outcomes while gain of NR4a1 enables stroke recovery in HSD animals. Together, we provide the first evidence that links HSD-induced innate immune memory to the acquisition of persistent dysregulated inflammatory responses and unveils NR4a1 as a potential therapeutic target.

[Expression and Clinical Significance of Cytokines and Lymphocyte Subsets in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To study the role of cytokines and lymphocyte subsets in the diagnosis, prognosis and efficacy evaluation of DLBCL patients, and the effects of Tislelizumab on immune function and cytokines in DLBCL patients. METHODS: Twenty-three patients with newly diagnosed DLBCL were selected as DLBCL group and 34 patients with megaloblastic anemia as the control group. The levels of peripheral blood cytokines IL-2, IL-4, IL-6, IL-10, TNF- α and IFN-γ by ELISA method. The levels of peripheral blood CD3+, CD4+, CD8+ T lymphocytes, B lymphocytes and NK cells， the ratio of CD4+/CD8+ were detected by flow cytometry. The levels of cytokins and lymphocyto subsets in DLBCL patients with different clinical data and different therapeutic effects were compared. RESULTS: The levels of cytokines IL-2, IL-6 and IL-10 in DLBCL group were significantly higher than those in control group, but there was no significant correlation between cytokine levels and age and gender. The higher IPI score, higher Ann Arbor stage, B symptoms, higher ß 2-MG, LDH and CRP levels, IL-6 and IL-10 levels were significantly higher, and IL-4 was also significantly higher in patients with high LDH levels. Compared with the ineffective group, the levels of IL-6 and IL-10 were significantly lower and the level of CD4+ T cells and the ratio of CD4+/CD8+ was significantly higher in the effective group before therapy. The levels of IL-6, IL-10 and B lymphocytes in the effective group decreased significantly after therapy compared to those before therapy. After 4 cycles of therapy, the level of IL-2 and the ratio of CD4+/CD8+ in the Tislelizumab group were significantly higher than those in the non-Tislelizumab group, and the level of CD8+ T cells was significantly lower than that in the non-Tislelizumab group(P<0.05). The level of B lymphocytes in both the Tislelizumab group and the non-Tislelizumab group after therapy was significantly lower than that before therapy. CONCLUSION: The expression of cytokines and lymphocyte subsets in peripheral blood of patients with DLBCL is abnormal, which is related to the severity, prognosis and therapeutic effect of the disease. Tislelizumab can improve the immune function of patients with DLBCL by affecting cytokines and lymphocyte subsets and strengthen anti-tumor immunity.

The Association between Dietary Sugar Intake and Nephrolithiasis: Results from National Health and Nutrition Examination Survey 2007-2018.

BACKGROUND: Dietary sugar intake is gradually considered a risk factor for many diseases. A sugary diet was positively associated with risk of nephrolithiasis, but the specific relationships remain undefined. OBJECTIVES: To determine associations between risk of nephrolithiasis and dietary sugar intake. METHODS: This cross-sectional study involved 21,590 participants based on the National Health and Nutrition Examination Survey from 2007 to 2018. Amounts of dietary sugar intake (g/d) were the main exposure, including total sugar intake, added sugar intake, and food sources. Associations were analyzed by logistic regression models and restricted cubic splines using complex weighted designs. RESULTS: Weighted mean intake [standard error] of total sugar and added sugar were 111.2 [2.0] g/d and 73.7 [1.9] g/d in participants with nephrolithiasis, respectively. In the fully adjusted regression model, compared to those in quartile 1, the population in quartile 4 of total sugar intake showed a significant risk of nephrolithiasis [odds ratio (OR): 1.23; 95% confidence interval (CI): 1.00-1.51]; OR for added sugar intake was 1.56 (95% CI: 1.25-1.94). The risks of nephrolithiasis increased steadily when total sugar and added sugar intake exceeded ∼150 g/d and 63 g/d in restricted cubic spline analyses, respectively. The highest sugar intake from beverages was associated with an increased risk of nephrolithiasis (OR for total sugar: 1.36; 95% CI: 1.07-1.72; OR for added sugar: 1.37; 95% CI: 1.09-1.73). Added sugar intake from meat, egg, and oil was significantly associated with risk of nephrolithiasis (quartile 4, OR: 1.22; 95% CI: 1.02-1.47), whereas total sugar intake from dairy products was in reverse (quartile 4, OR: 0.67; 95% CI: 0.54-0.82). CONCLUSIONS: Total and added sugar intake, sugar intake from beverages, and added sugar intake from meat, egg, and oil were associated with an increased risk of nephrolithiasis, whereas total sugar intake from dairy products was negatively associated.

Coexistence of diffuse large B-cell lymphoma, acute myeloid leukemia, and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient: A case report.

BACKGROUND: The Coexistence of myeloid and lymphoid malignancies is rare. Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies. Synchronous diagnoses of diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML), and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in the same patient have not been reported. Here we report one such case. CASE SUMMARY: An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL. The bone marrow and peripheral blood contained two groups of cells. One group of cells fulfilled the criteria of AML, and the other revealed the features of small B lymphocytic proliferative disorder, which we considered LPL/WM. Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells, including ATM deletion, CCND1 amplification, mutations of MYD88 (L265P) and TP53, WT1 overexpression, and fusion gene of BIRC2-ARAP1, as well as complex chromosomal abnormalities. The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis. CONCLUSION: The coexistence of DLBCL, AML, and untreated LPL/WM in the same patient is extremely rare, which probably results from multiple steps of genetic abnormalities. Asymptomatic LPL/WM might have occurred first, then myelodysplastic syndrome-related AML developed, and finally aggressive DLBCL arose. Therefore, medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.

Biosorption and biotransformation behaviours of veterinary antibiotics under aerobic livestock wastewater treatment processes.

To study the fate of veterinary antibiotics released from swine wastewater treatment plants (SWTP), 10 antibiotics were investigated in each unit of a local SWTP periodically. Over a 14-month period of field investigation into target antibiotics, it was confirmed that tetracycline, chlortetracycline, sulfathiazole, and lincomycin were used in this SWTP, with their presence observed in raw manure. Most of these antibiotics could be effectively treated by aerobic activated sludge, except for lincomycin, which was still detected in the effluent, with a maximum concentration of 1506 µg/L. In addition, the potential for removing antibiotics was evaluated using lab-scale aerobic sequencing batch reactors (SBRs) that were dosed with high concentrations of antibiotics. The SBR results, however, showed that both sulfonamides and macrolides, as well as lincomycin, can achieve 100% removal in lab-scale aerobic SBRs within 7 days. This reveals that the potential removal of those antibiotics in field aeration tanks can be facilitated by providing suitable conditions, such as adequate dissolved oxygen, pH, and retention time. Furthermore, the biosorption of target antibiotics was also confirmed in the abiotic sorption batch tests. Biotransformation and hydrolysis were identified as the dominant mechanism for removing negatively charged sulfonamides and positively charged antibiotics (macrolides and lincomycin) in SBRs. This is due to their relatively low sorption affinity (resulting in negligible to 20% removal) onto activated sludge in abiotic sorption tests. On the other hand, tetracyclines exhibited significant sorption behavior both onto activated sludge and onto soluble organic matters in swine wastewater supernatant, accounting for 70%-91% and 21%-94% of removal within 24 h, respectively. S-shape sorption isotherms with saturation were observed when high amounts of tetracyclines were spiked into sludge, with equilibrium concentrations ranging from 0.4 to 65 mg/L. Therefore, the sorption of tetracyclines onto activated sludge was governed by electrostatic interaction rather than hydrophobic partition. This resulted in a saturated sorption capacity (Qmax) of 17,263 mg/g, 1637 mg/g, and 641.7 mg/g for OTC, TC, and CTC, respectively.

The efficacy and safety of asleep and awake subthalamic deep brain stimulation for Parkinson's disease patients: A 1-year follow-up.

Introduction: Traditional DBS is usually conducted under local anesthesia (LA) which is intolerable to some patients, DBS under general anesthesia (GA) was opted to extended surgical indication. This study aimed to compare the efficacy and safety of bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) under asleep and awake anesthesia state in 1-year postoperative follow-up. Methods: Twenty-one PD patients were assigned to asleep group and 25 patients to awake group. Patients received bilateral STN-DBS under different anesthesia state. The PD participants were interviewed and assessed preoperatively and at 1-year postoperative follow-up. Results: At 1-year follow-up, compared surgical coordinate in two groups, the left-side Y of asleep group showed more posterior than awake group (Y was-2.39 ± 0.23 in asleep group, -1.46 ± 0.22 in awake group, p = 0.007). Compared with preoperative OFF MED state, MDS-UPDRS III scores in OFF MED/OFF STIM state remained unchanged, while in OFF MED/ON STIM state were significantly improved in awake and asleep groups, yet without significant difference. Compared with preoperative ON MED state, MDS-UPDRS III scores in ON MED/OFF STIM, and ON MED/ON STIM state remained unchanged in both groups. In non-motor outcomes, PSQI, HAMD, and HAMA score significantly improved in asleep group compared to awake group at 1-year follow-up (PSQI, HAMD, and HAMA score in 1-year follow-up were 9.81 ± 4.43; 10.00 ± 5.80; 5.71 ± 4.75 in awake group, 6.64 ± 4.14; 5.32 ± 3.78; 3.76 ± 3.87 in asleep group, p = 0.009; 0.008; 0.015, respectively), while there was no significant difference in PDQ-39, NMSS, ESS, PDSS score, and cognitive function. Anesthesia methods was significantly associated with improvement of HAMA and HAMD score (p = 0.029; 0.002, respectively). No difference in LEDD, stimulation parameters and adverse events was observed between two groups. Discussion: Asleep STN-DBS may be considered a good alternative method for PD patients. It is largely consistent with awake STN-DBS in motor symptoms and safety. Yet, it showed higher improvement in terms of mood and sleep compared to awake group at 1-year follow-up.

A Methodology for Enhancing SSVEP Features Using Adaptive Filtering Based on the Spatial Distribution of EEG Signals.

In this paper, we propose a classification algorithm of EEG signal based on canonical correlation analysis (CCA) and integrated with adaptive filtering. It can enhance the detection of steady-state visual evoked potentials (SSVEPs) in a brain-computer interface (BCI) speller. An adaptive filter is employed in front of the CCA algorithm to improve the signal-to-noise ratio (SNR) of SSVEP signals by removing background electroencephalographic (EEG) activities. The ensemble method is developed to integrate recursive least squares (RLS) adaptive filter corresponding to multiple stimulation frequencies. The method is tested by the SSVEP signal recorded from six targets by actual experiment and the EEG in a public SSVEP dataset of 40 targets from Tsinghua University. The accuracy rates of the CCA method and the CCA-based integrated RLS filter algorithm (RLS-CCA method) are compared. Experiment results show that the proposed RLS-CCA-based method significantly improves the classification accuracy compared with the pure CCA method. Especially when the number of EEG leads is low (three occipital electrodes and five non occipital electrodes), its advantage is more significant, and accuracy reaches 91.23%, which is more suitable for wearable environments where high-density EEG is not easy to collect.

Direct Thermal Growth of Gold Nanopearls on 3D Interweaved Hydrophobic Fibers as Ultrasensitive Portable SERS Substrates for Clinical Applications.

Surface-enhanced Raman spectroscopy (SERS)-based biosensors have attracted much attention for their label-free detection, ultrahigh sensitivity, and unique molecular fingerprinting. In this study, a wafer-scale, ultrasensitive, highly uniform, paper-based, portable SERS detection platform featuring abundant and dense gold nanopearls with narrow gap distances, are prepared and deposited directly onto ultralow-surface-energy fluorosilane-modified cellulose fibers through simple thermal evaporation by delicately manipulating the atom diffusion behavior. The as-designed paper-based SERS substrate exhibits an extremely high Raman enhancement factor (3.9 × 1011 ), detectability at sub-femtomolar concentrations (single-molecule level) and great signal reproductivity (relative standard deviation: 3.97%), even when operated with a portable 785-nm Raman spectrometer. This system is used for fingerprinting identification of 12 diverse analytes, including clinical medicines (cefazolin, chloramphenicol, levetiracetam, nicotine), pesticides (thiram, paraquat, carbaryl, chlorpyrifos), environmental carcinogens (benzo[a]pyrene, benzo[g,h,i]perylene), and illegal drugs (methamphetamine, mephedrone). The lowest detection concentrations reach the sub-ppb level, highlighted by a low of 16.2 ppq for nicotine. This system appears suitable for clinical applications in, for example, i) therapeutic drug monitoring for individualized medication adjustment and ii) ultra-early diagnosis for pesticide intoxication. Accordingly, such scalable, portable and ultrasensitive fibrous SERS substrates open up new opportunities for practical on-site detection in biofluid analysis, point-of-care diagnostics and precision medicine.

Resolving the "health vs environment" dilemma with sustainable disinfection during the COVID-19 pandemic.

The overuse of disinfection during the COVID-19 pandemic leads to an emerging "health versus environment" dilemma that humans have to face. Irresponsible and unnecessary disinfection should be avoided, while comprehensive evaluation of the health and environmental impacts of different disinfectants is urgently needed. From this discussion, we reach a tentative conclusion that hydrogen peroxide is a green disinfectant. Its on-demand production enables a circular economy model to solve the storage issues. Water, oxygen, and electrons are the only feedstock to generate H2O2. Upon completion of disinfection, H2O2 is rapidly converted back into water and oxygen. This model adopts several principles of green chemistry to ensure overall sustainability along the three stages of its whole life cycle, i.e., production, disinfection, and decomposition. Physical methods, particularly UV irradiation, also provide sustainable disinfection with minimal health and environmental impacts.

Chronic endometritis impairs embryo implantation in patients with repeated implantation failure: A retrospective study.

OBJECTIVE: To assess whether chronic endometritis (CE) affects embryo implantation in patients with repeated implantation failure (RIF). MATERIALS AND METHODS: We retrospectively analyzed 126 RIF patients who were never diagnosed with CE and received no prior antibiotic therapy. Endometrial specimens obtained by endometrial scratching during mid-luteal phase were immunostained by CD138, a hallmark plasmacyte marker, to identify CE. Pregnancy outcome in RIF patients who underwent IVF-ET frozen-embryo within transfers 6 months after endometrial scratching was compared between women with and without CE. RESULTS: The prevalence of CE in patients with RIF was found to be 11.9% (15/126). Moreover, a significantly reduced clinical pregnancy rate was observed in RIF patients with CE (20% vs. 46.85%; p = 0.04). The live birth rate also exhibited a decreasing trend in RIF patients with CE, although there was no statistically significant difference (20% vs. 41.58%; p = 0.109). CONCLUSIONS: CE may be involved in the failure of embryo implantation and reduced clinical pregnancy outcome in patients with RIF.

Visible-Light Driven H2O-to-H2O2 Reaction by Nitrogen-Enriched Resins for Photocatalytic Oxidation of an Organic Pollutant in Wastewater.

A photocatalytic H2O-to-H2O2 reaction for sustainable organic wastewater treatment is environmentally attractive. Phenolic resins, inexpensive metal-free photocatalysts, are capable of harvesting visible light. Herein, novel nitrogen-enriched resin photocatalysts with a desired band-gap energy (1.83-1.98 eV) for harvesting visible light were prepared by copolymerization of resorcinol and melem for simultaneous photocatalytic H2O-to-H2O2 and oxidation of methylene blue. Under visible light irradiation for 5 h, very high yields of H2O2 (870-975 µM of H2O2/g/h) by RFM resin photocatalysts could be achieved. The photocatalytic H2O2 for reactive oxygen species (•OH) and photogenerated h+ could account for high conversion (40% conversion under visible light irradiation within 3 h) in oxidation of methylene blue. Such unique low-cost metal-free resins demonstrate the visible light photocatalytic H2O-to-H2O2 reaction which can synergize with the oxidation of organic pollutants in wastewater.

A case of systemic mastocytosis mimicking POEMS syndrome: A case report.

RATIONALE: POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome is a rare and complicated disease related to multiple organs and systems. Here, we report a case of systemic mastocytosis (SM) that was misdiagnosed as a POEMS syndrome. PATIENT CONCERNS: A 42-year-old man presented with skin changes, diarrhea, and limb numbness. DIAGNOSES: Positron emission tomography/computed tomography revealed extravascular volume overload, organomegaly, lymphadenopathy, and bone lesions with mixed lesions of osteosclerosis and osteolysis. Therefore, POEMS syndrome was suspected. Further histopathological and immunohistochemical examination of the bone marrow, lymph nodes, and gastric mucosa suggested a diagnosis of mastocytosis. The c-Kit D816V mutation confirmed the diagnosis of SM. INTERVENTIONS: The patient received the treatment of pegylated interferon-alpha weekly and glucocorticoid daily. OUTCOMES: The symptoms relieved significantly. LESSONS: There are many similar features between POEMS syndrome and SM, probably leading to misdiagnosis. This study analyzed the different points between them which can provide help for differentiation.

Eight-year follow-up outcome of subthalamic deep brain stimulation for Parkinson's disease: Maintenance of therapeutic efficacy with a relatively low levodopa dosage and stimulation intensity.

AIMS: This follow-up study aimed to examine the 8-year efficacy and safety of subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with Parkinson's disease (PD) in southern China. METHODS: The follow-up data of 10 patients with PD undergoing STN-DBS were analyzed. Motor symptoms were assessed before and 1, 3, 5, and 8 years after the surgery with stimulation-on in both off-medication (off-med) and on-medication (on-med) status using the Unified Parkinson's disease Rating Scale Part III. The quality of life was assessed using the 39-item Parkinson's Disease Questionnaire. The sleep, cognition, and emotion were evaluated using a series of nonmotor scales. Levodopa equivalent daily dose (LEDD) and stimulation parameters were recorded at each follow-up. RESULTS: The motor symptoms were improved by 50.9%, 37.7%, 36.7%, and 37.3% in 1, 3, 5, and 8 years, respectively, in the off-med / stimulation-on status compared with the baseline. The quality of life improved by 39.7% and 56.1% in 1 and 3 years, respectively, but declined to the preoperative level thereafter. The sleep, cognition, and emotion were mostly unchanged. LEDD reduced from 708.1 ± 172.5 mg to 330 ± 207.8 mg in 8 years. The stimulation parameters, including amplitude, pulse width, and frequency, were 2.77 ± 0.49 V, 71.3 ± 12.8 µs, and 121.5 ± 21 Hz, respectively, in 8 years. CONCLUSION: Long-term therapeutic efficacy of STN-DBS could be achieved even with relatively low stimulation intensity and medication dosage for PD patients in southern China. Motor improvement and medication reduction were maintained through the 8-year follow-up, but improvement in quality of life lasted for only 3 years. No definite changes was found in nonmotor symptoms after STN-DBS.

Robust O2 Supplementation from a Trimetallic Nanozyme-Based Self-Sufficient Complementary System Synergistically Enhances the Starvation/Photothermal Therapy against Hypoxic Tumors.

Much effort has been focused on novel nanomedicine for cancer therapy. However, tumor hypoxia limits the efficacy of various cancer therapeutics. Herein, we constructed a self-sufficient hybrid enzyme-based silk fibroin hydrogel system, consisting of Pt-decorated hollow Ag-Au trimetallic nanocages (HGN@Pt) and glucose oxidase (GOx), to supply O2 continuously and consume glucose concurrently and, thereby, synergistically enhance the anti-cancer efficacy of a combined starvation and photothermal therapy operating in a hypoxic tumor microenvironment. Thanks to the cooperative effects of the active surface atoms (resulting from the island-like features of the Pt coating), the intrinsically hollow structure, and the strain effect induced by the trimetallic composition, HGN@Pt displayed efficient catalase-like activity. The enhancement in the generation of O2 through the decomposition of H2O2 mediated by the as-designed nanozyme was greater than 400% when compared with that of hollow Ag-Pt bimetallic nanospheres or tiny Pt nanoparticles. Moreover, in the presence of HGN@Pt, significant amounts of O2 could be generated within a few minutes, even in an acidic buffer solution (pH 5.8-6.5) containing a low concentration of H2O2 (100-500 µM). Because HGN@Pt exhibited a strong surface plasmon resonance peak in the near-infrared wavelength range, it could be used as a photothermal agent for hyperthermia therapy. Furthermore, GOx was released gradually from the SF hydrogel into the tumor microenvironment to mediate the depletion of glucose, leading to glucose starvation-induced cancer cell death. Finally, the O2 supplied by HGN@Pt overcame the hypoxia of the microenvironment and, thereby, promoted the starvation therapeutic effect of the GOx-mediated glucose consumption. Meanwhile, the GOx-produced H2O2 from the oxidation of glucose could be used to regenerate O2 and, thereby, construct a complementary circulatory system. Accordingly, this study presents a self-sufficient hybrid enzyme-based system that synergistically alleviates tumor hypoxia and induces an anti-cancer effect when combined with irradiation of light from a near-infrared laser.

Inhibition of Retinal Ganglion Cell Loss By a Novel ROCK Inhibitor (E212) in Ischemic Optic Nerve Injury Via Antioxidative and Anti-Inflammatory Actions.

Purpose: This study investigated the neuroprotective effects of administration of ROCK inhibitor E212 on ischemic optic neuropathy. Methods: Rats received an intravitreal injection of either E212 or PBS immediately after optic nerve infarct. The oxidative stress in the retina was detected by performing superoxide dismutase activity and CellROX assays. The integrity of retinal pigment epithelium was determined by staining of zona occludens 1. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined by using flash visual-evoked potential analysis, retrograde FluoroGold labeling, and TdT-dUTP nick end-labeling assay. Macrophage infiltration was detected by staining for ED1. The protein levels of TNF-α, p-CRMP, p-AKT1, p-STAT3, and CD206 were evaluated using Western blotting. Results: Administration of E212 resulted in a 1.23-fold increase in the superoxide dismutase activity of the retina and 2.28-fold decrease in RGC-produced reactive oxygen species as compared to the levels observed upon treatment with PBS (P < 0.05). Moreover, E212 prevented the disruption of the blood-retinal barrier (BRB) in contrast to PBS. The P1-N2 amplitude and RGC density in the E212-treated group were 1.75- and 2.05-fold higher, respectively, than those in the PBS-treated group (P < 0.05). The numbers of apoptotic RGCs and macrophages were reduced by 2.93- and 2.54-fold, respectively, in the E212-treated group compared with those in the PBS-treated group (P < 0.05). The levels of p-AKT1, p-STAT3, and CD206 were increased, whereas those of p-PTEN, p-CRMP2, and TNF-α were decreased after treatment with E212 (P < 0.05). Conclusions: Treatment with E212 suppresses oxidative stress, BRB disruption, and neuroinflammation to protect the visual function in ischemic optic neuropathy.