RESUMEN

Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

Asunto(s)

RESUMEN

BACKGROUND AND OBJECTIVE: Asciminib is approved in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) treated with ≥ 2 prior tyrosine kinase inhibitors. Here, we aimed to demonstrate similarity in efficacy/safety of asciminib 80 mg once daily (q.d.) versus 40 mg twice daily (b.i.d.) in patients with CML-CP without T315I mutation and support the use of the 200-mg b.i.d. dosage in patients harboring T315I, using model-informed drug development. METHODS: Data were collected from 199 patients in the phase I (NCT02081378; 10-200 mg b.i.d. or 10-400 mg q.d.) and 154 patients in the phase III (NCT03106779; 40 mg b.i.d.) studies. Evaluations were based on population pharmacokinetics (PopPK) and exposure-response (efficacy/safety) analyses. RESULTS: PopPK showed comparable exposure (area under the curve, AUC0-24h) for 40 mg b.i.d. and 80 mg q.d. (12,638 vs 12,646 ng*h/mL); average maximum and minimum plasma concentrations for 80 mg q.d. were 1.61- and 0.72-fold those of 40 mg b.i.d., respectively. Exposure-response analyses predicted similar major molecular response rates for 40 mg b.i.d. and 80 mg q.d. (Week 24: 27.6% vs 24.8%; Week 48: 32.3% vs 30.6%). Results also established adequacy of 200 mg b.i.d. in patients with T315I mutation (Week 24: 20.7%; Week 48: 23.7%), along with a similar safety profile for all dose regimens. CONCLUSIONS: Similarity between 40 mg b.i.d. and 80 mg q.d. regimens was investigated, demonstrating similar and substantial efficacy with well-tolerated safety in patients without T315I mutation. The 200-mg b.i.d. dose was deemed safe and effective for patients with T315I mutation.

RESUMEN

BACKGROUND: Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) and the occurrence of peptic ulcers (PU). However, the precise causal relationship between these factors remains ambiguous. Consequently, this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer. AIM: To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) association with PU via genetic methods, guiding future clinical research. METHODS: Genome-wide association study (GWAS) datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk). For the forward Mendelian randomization (MR) analysis, 72 single nucleotide polymorphisms (SNPs) were identified as instrumental variables. These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL, with peptic ulcer as the outcome variable. Conversely, for the inverse MR analysis, no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome. All MR analyses utilized inverse variance weighted (IVW) as the primary analytical method. Additionally, weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects. Egger regression was used as a supplementary method to evaluate potential directional pleiotropy. Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing. RESULTS: The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer (IVW: OR = 2.557, 95%CI = 1.274-5.132, P = 0.008). However, no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis. CONCLUSION: In conclusion, our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers. However, further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.

RESUMEN

Multiple myeloma (MM) is a malignancy of plasma cells accompanied by immune dysfunction. This study aimed to provide a comprehensive and dynamic characterization of the peripheral immune environment in MM patients and find its diagnostic and prognostic values for therapy. The peripheral immune profiles of MM inpatients and healthy controls were assessed by flow cytometry. A longitudinal study of immune subsets was observed during cycles of chemotherapy. The diagnostic and prognostic models were established based on immune subsets by the absolute shrinkage and selection operator (LASSO) and multivariate regression. MM patients possessed an impeded immune landscape, including reduced activation of B cells, increased effective T cells and regulatory T cells (Tregs), augmented CD16 expression on monocytes and dendritic cell percentages, decreased CD56dimCD16+ natural killer cells (NKs), and amplified CD56bright and HLA-DR+ natural killer T cells (NKTs). Chemotherapy has different dynamic effects on specific cells, of which 2 cycles is the key turning point. NKT, dendritic cells, naïve Tc and Th cells, HLA-DR+ Tc cells, CD56dim NKTs, CD16++ monocytes, and CD25+ B cells could have the diagnostic value, and a prognostic model including neutrophils, naïve Tc cells, CD56brightCD16dim NKs, and CD16+ dendritic cells was established with acceptable accuracy. Our data showed dynamic and abnormal peripheral immune profiles in MM patients, which had prognostic values and could provide the basis for clinical therapy.

RESUMEN

Management of diabetic wounds becomes increasingly challenging as bacterial infections intensify the inflammation. Employing polysaccharide hydrogels with inherent antibacterial qualities can significantly reduce the need for antibiotics to manage infections in diabetic wounds. The typical approach to achieving antibacterial outcomes with hydrogels relies on the penetration of bacteria into their porous architecture. Such penetration not only takes time but can also prolong inflammation, thus impeding the healing of wounds. Hence, the quick capture and eradication of bacteria are essential for optimizing the hydrogel's antibacterial performance. Herein, we introduce a multifunctional polysaccharide hydrogel dressing-designated as HAQ-created for managing bacterial infections in diabetic wounds. This dressing is based on hyaluronic acid, which is modified with methacrylic anhydride, and special functional groups are added to the modified hyaluronic acid matrix: phenylboronic acid for capturing bacteria and quaternary ammonium chitosan for bacterial destruction. As expected, the HAQ system exhibits robust antibacterial effectiveness against both methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa in vitro and in vivo. Consequently, HAQ stands as a promising hydrogel dressing with intrinsic antibacterial capabilities and offers significant potential for managing diabetic wounds infected by drug-resistant bacteria.

RESUMEN

The commercialized genetically modified (GM) papaya cultivars have protected papaya from the devastating disease caused by papaya ringspot virus (PRSV). However, papaya leaf distortion mosaic virus (PLDMV), which causes similar infection symptoms but is serologically distinct from PRSV, was found as a competitive threat to the papaya industry. Our study surveyed the occurrence of PRSV and PLDMV as well as the transgenic markers of the 35S promoter from cauliflower mosaic virus (CaMV 35S) and the neomycin phosphotransferase II (NPT II) gene in feral papaya plants, which were found frequently growing outside of cultivated papaya fields on Hainan Island. In total, 123 feral papayas, comprising 62 (50.4%) GM plants and 61 (49.6%) non-GM ones, were sampled. Among them, 23 (18.7%) were positive for PRSV, 49 (39.8%) were positive for PLDMV, including 5 plants co-infected by PRSV and PLDMV, and 56 (45.5%) plants were free of either virus. In traditional papaya growing regions, we detected fewer PRSV-infected plants (2 in 33, 6%) than in other regions (21 in 90, 23%). But overall, whether transgenic or not made no significance in PRSV incidence (P=0.230), with 9 PRSV-infected plants among 62 GM papayas and 14 among 61 non-GM papayas. Phylogenetic and genetic differentiation analysis showed a clear correlation between PRSV and PLDMV populations and their geographical origins. Negative selection was estimated for the selected gene regions of both viruses. Notably, PLDMV has deviated from neutral evolution and experienced population expansion, exhibiting increased genetic diversity and is becoming the predominant threat to papaya in Hainan.

RESUMEN

As the global population ages, the incidence of Parkinson's Disease (PD) continues to rise, imposing significant social and economic burdens. Mangiferin (MGF), a polyphenolic, bioactive compound has been shown to play a role in the prevention and treatment of PD. This study investigates the neuroprotective effects of MGF in an MPTP-induced zebrafish model of PD through transcriptome analysis. Initially, optimal concentrations for modeling were determined using various MPTP and MGF combinations. The zebrafish were then divided into control, MPTP-treated, and MGF co-treated groups. Subsequent evaluations included hatching rates, mortality rates, growth and development conditions, spontaneous motor abilities, as well as measurements of enzymatic activities of SOD, CAT, and levels of GSH. Ultimately, the therapeutic efficacy of MGF on the PD model in zebrafish was assessed through transcriptome sequencing. The results demonstrated that MPTP treatment induced PD-associated symptoms in zebrafish, while MGF treatment significantly improved the motor abilities and survival rates of the PD model zebrafish, effectively reducing oxidative stress and ameliorating PD symptoms. Transcriptome sequencing further revealed that MGF may mitigate mitochondrial-related oxidative stress in PD zebrafish by modulating the expression of critical genes including lrrk2, vps35, atp13a, dnajc6, and uchl1. Differential gene expression analysis indicated that these genes are primarily involved in vital signaling pathways, such as neuroactive ligand-receptor interaction, and the calcium signaling pathway. In summary, our study provides robust scientific evidence supporting MGF as a potential therapeutic candidate for PD by preserving mitochondrial homeostasis and elucidating its mechanisms of action.

RESUMEN

BACKGROUND: Silica particles can cause silicosis, a disease characterized by diffuse fibrosis of the lungs. Various signaling pathways composed of different types of cells and cytokines are involved in the development of silicosis. Exosomes have become a research hotspot recently. However, the role of exosomal microRNA (miRNA) in silicosis remains unclear. METHODS: In this study, we generated exosomal miRNA sequences from exosomes isolated from bronchoalveolar lavage fluid (BALF) of silicosis patients and the control group by high-throughput sequencing. Functional annotation and analysis of miRNA identified key target miRNAs. Levels of target miRNAs were analyzed in patient and animal samples and cells. Effects of increased miRNA were assessed through protein levels in target signaling pathways in cells treated with silica, miRNA mimics, and inhibitors. RESULTS: Our study identified 40 up-regulated and 70 down-regulated miRNAs, with miR-552-3p and its putative target gene Caveolin 1 (CAV1) as targets for further research. We found that the levels of exosomal miR-552-3p increased in silicosis patients' BALF samples, silicosis model mice, and A549 cells exposed to silica. Inhibition of miR-552-3p suppressed the expression of fibrosis markers. The increased miR-552-3p leads to the up-regulation of fibronectin and α-smooth muscle actin (α-SMA) and the suppression of caveolin 1 in fibroblast cells. Mitogen-activated protein kinase (MAPK) signaling pathways are activated in cells treated with silica and miR-552-3p mimics. CONCLUSIONS: These results help to understand exosomal miRNA-mediated intercellular communication and its key role in fibroblast activation and silicosis.

RESUMEN

BACKGROUND: Knee septic arthritis (SA) and Lyme arthritis (LA) often have similar presentations but bacterial SA necessitates urgent surgery. Predictive factors for differentiating SA and other infectious/inflammatory conditions have been published. Our purpose was to test these algorithms using a retrospective multicenter musculoskeletal infection database. METHODS: Patients ≤18 years old with isolated knee SA or LA were identified. Diagnostic criteria for SA were synovial WBC count >50,000 cells/mm3, imaging with fluid aspiration suggestive of SA, or joint aspirate/tissue sample cultured positive for bacteria. Diagnostic criteria for LA was positive Lyme titer. Demographics, weightbearing status, admission vitals, and laboratory tests were collected. Predictive factors from Baldwin criteria for differentiating knee SA and LA, and Kocher criteria for differentiating hip SA and transient synovitis were tested. RESULTS: One hundred fifty-five patients (119 SA and 36 LA) were analyzed. Patients with SA were younger (2.2 vs. 8.0 y), more nonweightbearing (74% vs. 33%), had a higher pulse (127 vs. 106), and higher WBC (12.4 vs. 10.2) (all P<0.001).Baldwin criteria (pain with joint motion, history of fever, CRP >40 mg/L, age <2 y) were tested. Pain with motion was not collected in our database. Of the remaining factors, the probability of SA was 63% with 0 and 92% with 3 factors (AUC 0.64). Kocher criteria (nonweightbearing, temperature >101.3°F, WBC >12.0, ESR >40) and CRP >20 mg/L were also tested. The probability of SA was 41% with 0 and 96% with all factors (AUC 0.69).Using our cohort data, regression analysis with backward stepwise elimination determined that age <4 years, nonweightbearing, admission WBC >13.0, platelets <325, and ESR >70 were predictive factors for SA. The probability of SA with 0 factors was 16%, 1 factor 52%, 2 factors 86%, 3 factors 97%, and 4 factors 100% (AUC 0.86). CONCLUSIONS: Our model identified age <4 years, nonweightbearing, admission WBC >13.0, platelets <325, and ESR >70 as independent predictive factors for knee SA. The more factors present, the higher the likelihood of having SA versus LA. LEVEL OF EVIDENCE: Diagnostic level III.

RESUMEN

OBJECTIVE: To evaluate the effects of different intervention measures on duration of mechanical ventilation and the length of intensive care unit (ICU) stay in critically ill patients using network Meta-analysis. METHODS: Randomized controlled trial (RCT) on the effects of different intervention measures on duration of mechanical ventilation and the length of ICU stay in critically ill patients were systematically searched in PubMed, Embase, China Biomedical Literature Database, CNKI, and other databases. The search time limit was from the establishment of the database to November 2023. Literature screening, quality assessment, and data extraction were independently conducted by two researchers. Network Meta-analysis was employed to assess the effects of each intervention on duration of mechanical ventilation and the length of ICU stay, and funnel plots were generated. RESULTS: A total of 37 RCTs were included, involving 3 977 severe patients, 2 041 in the intervention group and 1 936 in the control group. Thirteen types of interventions were analyzed, including usual care (UC), early activity (EA), early comprehensive rehabilitation (ECR), early pulmonary rehabilitation (EPR), cluster intervention strategy (CS), sedation, analgesia and cluster nursing (SACN), music therapy (MT), neuromuscular electrical stimulation (NMES), modified education and visitation (MV), virtual reality (VR), auricular point sticking (APS), acupoint acupuncture (AA), and concerted intervention (COR). Network Meta-analysis showed that MV significantly better than COR [standardized mean difference (SMD) = -2.35, 95% confidence interval (95%CI) was -4.30 to -0.39], EPR (SMD = -2.59, 95%CI was -4.81 to -0.37), and UC (SMD = -4.10, 95%CI was -5.71 to -2.49) in improving duration of mechanical ventilation in critically ill patients. COR was significantly better than UC in shortened length of ICU stay (SMD = -5.72, 95%CI was -10.07 to -1.37). The efficacy ranking results showed that for duration of mechanical ventilation, the surface under the cumulative ranking curve (SUCRA) was highest for MV (85.4%) and EA (85.4%), followed by AA (74.9%), NMES (63.1%), ECR (51.7%), CS (48.8%), SACN (34.3%), COR (29.4%), EPR (26.1%), and UC (0.7%). For the length of ICU stay, COR had the highest SUCRA (82.3%), followed by APS (79.7%), MV (77.7%), EPR (68.0%), NMES (57.6%), CS (54.4%), ECR (51.1%), SACN (41.9%), MT (39.8%), EA (39.3%), AA (33.0%), VR (15.4%), and UC (9.8%). The funnel plot results of ICU stay showed that the publication bias between studies were relatively small. CONCLUSIONS: MV and COR appear to be effective interventions for reducing mechanical ventilation time and ICU stay in critically ill patients. However, due to the number and quality of included studies, these findings require confirmation through additional high-quality research.

Asunto(s)

RESUMEN

OBJECTIVES: To investigate the diagnostic value of iTrace visual function analyzer, Pentacam 3D anterior segment analysis system and Lens Opacities Classification System III (LOCS III) in assessing lens opacity in patients with age-related cataract (ARC). METHODS: A total of 129 patients with ARC admitted to Anonymized from May 2019 to April 2021 were selected as the research objects. The degree of lens opacity was evaluated by LOCS III classification, iTrace and anterior segment analysis. RESULTS: The Pentacam nucleus staging (PNS) grade was strongly correlated with nuclear color (NC) (r = 0.537, p < 0.05) and moderately correlated with nuclear opalescence (NO) (r = 0.473, p < 0.05). The integrated density (IntDen) in 3-mm nuclear region was strongly correlated with NC (r = 0.548, p < 0.05) and NO (r = 0.539, p < 0.05). The dysfunctional lens index (DLI) in 3-mm area was negatively correlated with NC (r=-0.252, p < 0.05), NO (r=-0.239, p < 0.05) and posterior subcapsular cataract (r=-0.271, p < 0.05). PNS was weakly negatively correlated with the DLI in 3-mm area (r=-0.219, p < 0.05), and IntDen in 3-mm core area was weakly negatively correlated with the DLI in 3-mm area (r=-0.291, p < 0.05). CONCLUSION: A combination of iTrace, anterior segment analysis and LOCS III may be beneficial in objectively assessing the opacity of different regions of the lens.

RESUMEN

Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.

Asunto(s)

RESUMEN

BACKGROUND: Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. METHODS: We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). RESULTS: After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01-1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44-4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20-3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22-4.41, p = 0.011), while WMH progression was primarily affected by BMI (ß = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (ß = -0.076, SE = 0.027, p = 0.019). CONCLUSIONS: Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.

Asunto(s)

RESUMEN

OBJECTIVE: Whether to continue administering immunotherapy to patients with advanced non-small cell lung cancer (NSCLC) who have experienced tumor progression remains controversial after immunotherapy. The aims were to explore survival outcomes after further immunotherapy post-progression and to determine the optimal combination therapy in such cases. METHODS: Overall, 507 patients with NSCLC who underwent immunotherapy and experienced tumor progression were retrospectively divided into Immuno-combination and No-immuno groups according to whether additional combination therapy involving immunotherapy was administered post-progression. Progression-free survival (PFS) and overall survival (OS) were evaluated. Subgroup analyses were performed according to the different treatment regimens for patients in the Immuno-combination group. RESULTS: After propensity score matching, there were 150 patients in the No-immuno group and 300 patients in the Immuno combination group. Superior PFS was observed in the Immuno-combination group compared with those in the No-immuno group (6-month PFS: 25.3 % vs. 60.6 %; 12-month PFS: 6.7 % vs. 24.4 %; P < 0.001). Similar intergroup differences were observed for OS (12-month OS: 22.3 % vs. 69.4 %; 18-month OS: 6.4 % vs. 40.4 %; P < 0.001). Superior PFS outcomes were observed in the Immuno+Antiangiogenic group compared with the Immuno+Chemo group (6-month PFS: 51.3 % vs. 71.5 %; 12-month PFS: 23.1 % vs. 25.7 %; P = 0.017). Similar differences in OS were observed between those same subgroups (12-month OS: 62.1 % vs. 77.9 %; 18-month OS: 33.3 % vs. 48.7 %; P = 0.006). CONCLUSION: Patients with NSCLC experiencing tumor progression post-immunotherapy can still benefit from further treatment, with immunotherapy combined with antiangiogenic therapy the most efficacious option.

RESUMEN

Alzheimer's disease (AD) is a common neurodegenerative disease with the main manifestations of progressive cognitive dysfunction,behavioral disorders,and gradual decline of living ability.The etiology of AD is complex,and the pathogenesis of this disease remains controversial.Calcium signaling plays an important role in regulating neuronal activities,including neurotransmitter release,synaptic plasticity,memory storage,and neuronal apoptosis.Increasing studies have shown that neuronal calcium dyshomeostasis is a major pathological factor in the occurrence and development of AD.This article reviews the role and research progress in intracellular calcium dyshomeostasis in AD,including the relationship between calcium homeostasis and amyloid ß,the role of calcium/calmodulin-dependent protein kinases in tau phosphorylation,calcium signaling pathways,the relationship between calcium homeostasis and mitochondrial function,autophagy,and neuroinflammation.

Asunto(s)

RESUMEN

Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of m1A in dinoflagellate mRNA and shows that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3'UTRs, dinoflagellate mRNA m1A levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA m1A levels. Our data suggest that distinctive patterns of m1A modification might influence the expression of metabolism-related genes through translational control.

RESUMEN

Quasi-two-dimensional (Q-2D) perovskites show great potential in the field of photonic and optoelectronic device applications. However, defects and local lattice dislocation still limit performance and stability improvement by nonradiative recombination, unpreferred phase distribution, and unbonded amines. Here, a low-temperature synergistic strategy for both reconstructing and solidifying the perovskite top and buried interface is developed. By post-treating the 1,4-phenylenedimethanammonium (PDMA) based (PDMA)MA4Pb5I16 films with cesium acetate (CsAc) before thermal annealing, a condensation reaction between R-COO- and -NH2 and ion exchange between Cs+ and MA+ occur. It converts the unbonded amines to amides and passivates uncoordinated Pb2+. Meanwhile, it adjusts film composition and improves the phase distribution without changing the out-of-plane grain orientation. Consequently, performance of 18.1% and much-enhanced stability (e.g., stability for photo-oxygen increased over 10 times, light-thermal for T90 over 4 times, and reverse bias over 3 times) of (PDMA)MA4Pb5I16 perovskite solar cells are demonstrated.

RESUMEN

Background and purpose: Nowadays, myopia has become a highly prevalent disease globally, especially in East Asia. Epidemiological studies have found that there may be sex differences in the occurrence and progression of myopia, with females having a higher incidence of myopia and higher risk of myopia progression. The purpose of this study was to explore the sex differences in myopic cornea using corneal stroma removed by small incision lenticule extraction (SMILE) surgery. Methods: The corneal stroma of females with high myopia (FH) and males with high myopia (MH) were subjected to proteomic assays. Proteomic-related data were statistically analyzed using software such as MaxQuan, KAAS, Proteome Discovery, etc. The total number of proteins in the cornea and the proteins specifically expressed in the two groups were counted, and the differentially expressed proteins in the two groups were identified by expression fold change >2 and p-value <0.05, and volcano plots were constructed, and functional enrichment analysis, subcellular organelle analysis, and molecular interaction were implemented. Results: Ten samples from each group were analyzed. Twenty-seven proteins were down-regulated and 27 proteins were up-regulated in the FH group, of which 23 proteins were up-regulated in the range of 2-10-fold and 4 proteins were up-regulated in the range of >10-fold. Comparative proteomic analysis of the cornea of male and female patients with high myopia revealed that the expression of corneal extracellular matrix and collagen I, III, V, and VIII-associated proteins were increased in the cornea of female patients, and the transforming growth factor-ß (TGF-ß)/Smad pathway was an important pathway obtained by functional analysis. Conclusion: Comparative proteomic analysis of cornea from male and female patients with high myopia revealed increased expression of proteins related to extracellular matrix and collagen I, III, V, and VIII in female patients, and the TGF-ß/Smad pathway was an important pathway obtained from the functional analysis, suggesting that extracellular matrix remodeling and collagen fiber synthesis may be more active in the cornea of female patients.

RESUMEN

Epstein-Barr virus (EBV), an oncogenic herpesvirus, is predominantly found in the latent infection form and is highly associated with many human malignancies, which mainly have poor prognoses and no effective treatments. Here, we obtained thirteen compounds from small-molecule libraries for specific inhibition of EBV-latently infected cell growth in vitro by high-throughput screening. Among them, cetrimonium bromide (CetB) was identified to selectively inhibit the growth of different EBV-infected B lymphoma cell lines. Importantly, CetB reduced EBNA1 protein stability, activated G1 arrest and early apoptosis of EBV-latently infected cells without viral lytic reactivation, which leads to dramatically inhibit colony formation and tumor growth of EBV-infected cells in vitro and in vivo, and significantly prolong the survival of tumor-bearing mice. Overall, these findings demonstrate that CetB acts as a highly selective inhibitor of the growth of EBV-infected cells and has the potential for further development of effective therapeutic strategies specific against EBV-associated cancers.