Vertically Oriented Perovskites with Minimized Intrinsic Boundaries for Efficient Photovoltaics.

Intrinsic boundaries formed by grain stacks of randomly oriented perovskite crystallites seriously restrict charge transport in the resultant photovoltaic devices, whereas direct passivation of these defects remains unexplored, and it is desirable to modulate perovskite growth with uniform orientation. Herein, we report a simple but effective method to regulate perovskite crystallization by employing a volatile and polymerizable monomer of hydroxyethyl methacrylate (HEMA), which can simultaneously interact with both FA+ and Pb2+ via hydrogen and coordination bonding, respectively, to seed perovskite crystallization with accelerated nucleation and retarded crystal growth. Upon thermal annealing, the gradual volatilization and partial self-condensation of the HEMA drive the perovskite growth perpendicularly to the substrate, leading to largely suppressed defect states, improved crystallinity, and a reduced Young's modulus of the perovskite film. As a result, champion efficiencies exceeding 24 and 22% with improved operational and mechanical stability of the optimized perovskite solar cells based on rigid and flexible substrates were finally achieved.

Baicalin reduces inflammation to inhibit lung cancer via targeting SOCS1/NF-κB/STAT3 axis.

Inflammation affects several aspects of lung cancer progression including cell proliferation, metastasis, apoptosis, angiogenesis, and drug resistance. Baicalin, an active component of Scutellaria baicalensis Georgi, exhibits anticancer activity in various cancers. However, the effects of baicalin on lung cancer and the underlying molecular mechanisms remain largely unknown. This study is to explore the effect and mechanism of baicalin on lung cancer cell A549 and urethane-induced mouse lung cancer. A cell viability assay, colony formation assay, wound healing assay, acridine orange/ethidium bromide (AO/EB) staining assay, Western blot assay, urethane-induced mouse lung cancer model, hematoxylin and eosin (HE) staining, immunohistochemistry (IHC), and ELISA assay were performed to investigate the effects of baicalin on lung cancer in vitro and in vivo. Network pharmacology analysis, molecular docking, gene silencing assays, and LPS-induced inflammation model were utilized to explore the molecular mechanisms underlying the effect of baicalin on lung cancer. Baicalin showed significant anti-proliferative, anti-migratory, anti-inflammatory and pro-apoptotic effects in vitro; it also inhibited the progression of urethane-induced mouse lung cancer in vivo. Mechanistically, suppressor of cytokine signaling 1 (SOCS1) was the key determinant for baicalin-induced inhibition of lung cancer. Baicalin increased SOCS1 expression to inactivate the NF-κB/STAT3 pathway to inhibit lung cancer in vitro and in vivo. Taken together, baicalin reduces inflammation to inhibit lung cancer via targeting SOCS1/NF-κB/STAT3 axis, providing a prospective compound and novel target for lung cancer treatment.

Research progress on oncoprotein hepatitis B X­interacting protein (Review).

Hepatitis B X­interacting protein (HBXIP) is a membrane protein located on the lysosomal surface and encoded by the Lamtor gene. It is expressed by a wide range of tumor types, including breast cancer, esophageal squamous cell carcinoma and hepatocellular carcinoma, and its expression is associated with certain clinicopathological characteristics. In the past decade, research on the oncogenic mechanisms of HBXIP has increased and the function of HBXIP in normal cells has been gradually elucidated. In the present review, the following was discussed: The normal physiological role of the HBXIP carcinogenic mechanism; the clinical significance of high levels of HBXIP expression in different tumors; HBXIP regulation of transcription, post­transcription and post­translation processes in tumors; the role of HBXIP in improving the antioxidant capacity of tumor cells; the inhibition of ferroptosis of tumor cells and regulating the metabolic reprogramming of tumor cells; and the role of HBXIP in promoting the malignant progression of tumors. In conclusion, the present review summarized the existing knowledge of HBXIP, established its carcinogenic mechanism and discussed future related research on HBXIP.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis.

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment. Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies. Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13-4.82, P = 0.02). Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid.

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (ß = -0.18, 95%CI: -0.29 - -0.07, P = 0.002) and progressive motility (ß = -0.27, 95%CI: -0.43 - -0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: ß = 0.26, 95%CI: 0.01 - -0.51, Pinteraction = 0.047; progressive motility: ß = 0.64, 95%CI: 0.23 - 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

Dietary antioxidant intake is associated with heart failure: Results from the NHANES 2003-2019.

BACKGROUND: Growing evidence has shown that antioxidant diets protect against heart failure (HF). However, the association between the composite dietary antioxidant index (CDAI), an important measure of overall antioxidants in the diet, and HF has received little attention. OBJECTIVE: The purpose of this study was to examine the relationship between the CDAI and HF. METHODS: A secondary cross-sectional analysis of the 2003 to 2019 National Health and Nutrition Examination Survey (NHANES) was performed. Weighted multivariable logistic regression was used to test the association between the CDAI and HF in four different models, with subgroup analysis and an interaction test subsequently performed. RESULTS: A total of 37,390 participants were included. The HF groups had lower CDAI levels than those in the non-HF group (0.29 ± 0.04 vs. -0.74 ± 0.16, p < 0.0001). After adjusting for demographic characteristics, lifestyle factors, and disease history, a negative association was found between the CDAI and HF (OR: 0.97, 95 % CI: 0.94, 1.00). There was an inverse trend whereby increasing the CDAI was associated with decreasing the odds of HF (p for trend < 0.001). The subgroup analysis and interaction test showed no significant dependence on demographic characteristics, lifestyle factors, and disease history with regard to this association (all p for interaction > 0.05). CONCLUSION: The CDAI was inversely associated with HF in US adults, with higher CDAI levels possibly being associated with a lower incidence of HF, suggesting that dietary antioxidants may help prevent HF.

Protective effect of alizarin on vascular endothelial dysfunction via inhibiting the type 2 diabetes-induced synthesis of THBS1 and activating the AMPK signaling pathway.

BACKGROUND: In this study, we investigated the protective effects of alizarin (AZ) on endothelial dysfunction (ED). AZ has inhibition of the type 2 diabetes mellitus (T2DM)-induced synthesis of thrombospondin 1 (THBS1). Adenosine 5'-monophosphate- activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. PURPOSE: The aim of this study was to investigate the ameliorative effect of AZ on vascular injury caused by T2DM and to reveal the potential mechanism of AZ in high glucose (HG)-stimulated human umbilical vein endothelial cells (HUVECs) and diabetic model rats. STUDY DESIGN: HUVECs, rats and AMPK-/- transgenic mice were used to investigate the mitigating effects of AZ on vascular endothelial dysfunction caused by T2DM and its in vitro and in vivo molecular mechanisms. METHODS: In type 2 diabetes mellitus rats and HUVECs, the inhibitory effect of alizarin on THBS1 synthesis was verified by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB) so that increase endothelial nitric oxide synthase (eNOS) content in vitro and in vivo. In addition, we verified protein interactions with immunoprecipitation (IP). To probe the mechanism, we also performed AMPKα2 transfection. AMPK's pivotal role in AZ-mediated prevention against T2DM-induced vascular endothelial dysfunction was tested using AMPKα2-/- mice. RESULTS: We first demonstrated that THBS1 and AMPK are targets of AZ. In T2DM, THBS1 was robustly induced by high glucose and inhibited by AZ. Furthermore, AZ activates the AMPK signaling pathway, and recoupled eNOS in stressed endothelial cells which plays a protective role in vascular endothelial dysfunction. CONCLUSIONS: The main finding of this study is that AZ can play a role in different pathways of vascular injury due to T2DM. Mechanistically, alizarin inhibits the increase in THBS1 protein synthesis after high glucose induction and activates AMPKα2, which increases NO release from eNOS, which is essential in the prevention of vascular endothelial dysfunction caused by T2DM.

Application of TiLOOP bra in implant-based breast reconstruction is associated with decreased complication risk compared with other meshes: A systematic review and meta-analysis.

BACKGROUND: TiLOOP bra has been used for over 15 years, however, evidence regarding its safety in implant-based breast reconstruction (IBBR) for patients with breast cancer after mastectomy is still limited. We performed this meta-analysis to evaluate its risks and benefits in IBBR comparing with other meshes. METHODS: Electronic databases were searched to identify relevant studies comparing postoperative complications between TiLOOP bra and other reconstruction techniques in IBBR with or without meshes. We also compared patient satisfaction in physical well-being between two groups. Risk ratios (RRs) and mean differences with 95% confidence interval (CI) were calculated. RESULTS: Seven studies representing 1203 cases were analyzed. Compared with other meshes, the use of TiLOOP bra significantly reduced the risk of infection (RR = 0.53, 95% CI, 0.32-0.86), seroma (RR = 0.21, 95% CI, 0.07-0.61), red breast syndrome (RR = 0.10, 95% CI, 0.02-0.45), and capsular contracture (RR = 0.20, 95% CI, 0.05-0.75). Patient satisfaction in physical well-being was comparable between two groups. CONCLUSIONS: TiLOOP bra in IBBR has a favored safety profile over other meshes, which significantly reduced postoperative complication risk and did not affect patient satisfaction. Although prospective well-designed controlled studies are still warranted, TiLOOP bra is safe and reliable at present.

Joint Efforts of Replicative Helicase and SSB Ensure Inherent Replicative Tolerance of G-Quadruplex.

G-quadruplex (G4) is a four-stranded noncanonical DNA structure that has long been recognized as a potential hindrance to DNA replication. However, how replisomes effectively deal with G4s to avoid replication failure is still obscure. Here, using single-molecule and ensemble approaches, the consequence of the collision between bacteriophage T7 replisome and an intramolecular G4 located on either the leading or lagging strand is examined. It is found that the adjacent fork junctions induced by G4 formation incur the binding of T7 DNA polymerase (DNAP). In addition to G4, these inactive DNAPs present insuperable obstacles, impeding the progression of DNA synthesis. Nevertheless, T7 helicase can dismantle them and resolve lagging-strand G4s, paving the way for the advancement of the replication fork. Moreover, with the assistance of the single-stranded DNA binding protein (SSB) gp2.5, T7 helicase is also capable of maintaining a leading-strand G4 structure in an unfolded state, allowing for a fraction of T7 DNAPs to synthesize through without collapse. These findings broaden the functional repertoire of a replicative helicase and underscore the inherent G4 tolerance of a replisome.

Mollugin prevents CLP-induced sepsis in mice by inhibiting TAK1-NF-κB/MAPKs pathways and activating Keap1-Nrf2 pathway in macrophages.

Sepsis is a life-threatening organ dysfunction associated with macrophage overactivation. Targeted therapy against macrophages is considered a promising strategy for sepsis treatment. Mollugin (MLG), a compound extracted from traditional Chinese medicine Rubia cordifolia L., possesses anti-tumor and anti-inflammatory activities. This study aimed to investigate the anti-inflammatory effects and mechanisms of MLG in macrophages and its therapeutic role in CLP-induced sepsis in mice. The results demonstrated that MLG downregulated the inflammatory response induced by LPS or tumor necrosis factor α (TNF-α) in macrophages. Mechanistically, MLG suppressed the phosphorylation of TAK1, the upstream modulator of IKKα/ß and MAPKs, thereby inhibiting the pro-inflammatory signaling transduction of NF-κB and MAPKs. Additionally, MLG also activated the Nrf2 antioxidant pathway, reducing intracellular reactive oxygen species. CETSA and molecular docking analyses revealed that MLG could effectively bind to TAK1 and Keap1, which may be involved in the inhibition of TAK1- NF-κB/MAPKs and activation of Nrf2 mediated by MLG. Animal study demonstrated that MLG ameliorated inflammatory injury of lung and liver in CLP-induced sepsis mice probably by reducing the levels of pro-inflammatory cytokines. Therefore, our study suggests that bi-directional roles of MLG in improving sepsis via blocking the TAK1-NF-κB/MAPKs and activating Nrf2 pathways, indicating its potential as a promising candidate drug for sepsis treatment.

Case report: Supratherapeutic tacrolimus concentrations with nirmatrelvir/ritonavir in a lung transplant patient: a case report using Rifampin for reversal.

Paxlovid (nirmatrelvir/ritonavir) is an antiviral drug used to treat COVID-19, nirmatrelvir, a SARS-CoV-2 main protease inhibitor, works by inhibiting viral replication in the early stages, and ritonavir is a strong cytochrome P450 (CYP) 3A inhibitor that helps the nirmatrelvir reach and maintain the therapeutic concentrations. Paxlovid has a potential risk of drug interaction by elevating the plasma concentration of other drugs metabolized by CYP3A, like tacrolimus. This report examines the case of a 57-year-old female lung transplant patient self-administered Paxlovid for 5 days without discontinuing tacrolimus. She presented to the hospital with symptoms of headache, dizziness, palpitations, abdominal distension, nausea, vomiting, and diarrhea. The patient presented with tacrolimus toxicity and the blood concentration of tacrolimus was measured at 106 ng/mL. Urgent medical intervention was initiated, and Rifampin was administered to induce enzyme activity and rapidly decrease the concentration of tacrolimus. By adjusting the tacrolimus dosage, the final concentration was brought within the appropriate range. Clinical pharmacists should prioritize medication education for transplant patients to prevent severe drug interactions and minimize the impact on the patient's overall well-being.

E2F8 exerts cancer-promoting effects by transcriptionally activating RRM2 and E2F8 knockdown synergizes with WEE1 inhibition in suppressing lung adenocarcinoma.

Ribonucleotide reductase (RR) is a rate-limiting enzyme that facilitates DNA replication and repair by reducing nucleotide diphosphates (NDPs) to deoxyribonucleotide diphosphates (dNDPs) and is thereby crucial for cell proliferation and cancer development. The E2F family of transcription factors includes key regulators of gene expression involved in cell cycle control. In this study, E2F8 expression was significantly increased in most cancer tissues of lung adenocarcinoma (LUAD) patients and was correlated with the expression of RRM2 through database and clinical samples analysis. The protein expression of E2F8 and RRM2 were positively correlated with tumor-node-metastasis (TNM) pathological stage, and high expression of E2F8 and RRM2 predicted a low 5-year overall survival rate in LUAD patients. Overexpression and knockdown experiments showed that E2F8 was essential for LUAD cell proliferation, DNA synthesis, and cell cycle progression, which were RRM2-dependent. Reporter gene, ChIP-qPCR, and DNA pulldown-Western blot assays indicated that E2F8 activated the transcription of the RRM2 gene by directly binding with the RRM2 promoter in LUAD cells. Previous studies indicated that inhibition of WEE1 kinase can suppress the phosphorylation of CDK1/2 and promote the degradation of RRM2. We further showed here that the combination of E2F8 knockdown with MK-1775, an inhibitor of WEE1 being evaluated in clinical trials, synergistically suppressed proliferation and promoted apoptosis of LUAD cells in vitro and in vivo. Thus, this study reveals a novel role of E2F8 as a proto-oncogenic transcription activator by activating RRM2 expression in LUAD, and targeting both the transcription and degradation mechanisms of RRM2 could produce a synergistic inhibitory effect for LUAD treatment in addition to conventional inhibition of RR enzyme activity.

ADCY6 is a potential prognostic biomarker and suppresses OTSCC progression via Hippo signaling pathway.

Oral tongue squamous cell carcinoma (OTSCC) is a malignant tumor. Recently, studies have found that adenylate cyclase 6 (ADCY6) plays a pivotal role in many lethal tumors formation processes. The role of ADCY6 in OTSCC remains unknown. The expression of ADCY6 in OTSCC tissue samples was detected. The clinical significance of ADCY6 in OTSCC was analyzed by statistical methods. OTSCC cell lines were selected to analyze the biological function of ADCY6. Meanwhile, the effect of ADCY6 on the growth of OTSCC in vivo was explored using subcutaneous tumorigenesis assay. WB assay was used to detect the underlying signaling pathway. Cell function recovery test used to investigate the mechanism of ADCY6-promoting OTSCC malignant biological behavior via Hippo signaling pathway. We report that ADCY6 was obviously downregulated in OTSCC tissue samples and cell lines. Importantly, lower expression of ADCY6 indicates a poorer prognosis in patients with OTSCC, and its expression is significantly correlated with TNM stage and tumor size. Functionally, forced expression of ADCY6 can significantly inhibit the proliferation, migration, invasion, and promote apoptosis of OTSCC cells. Mechanistically, we demonstrated that ADCY6 upregulation impaired Hippo signaling pathway to reduce the malignant biological behavior of OTSCC. Generally, our findings suggest that ADCY6 suppressed Hippo signaling pathway to regulate malignant biological behavior in OTSCC, which provide new cues for further exploring the mechanism of occurrence and development of OTSCC.

Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis.

PURPOSE: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. METHODS: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People's Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. RESULTS: In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205-13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. CONCLUSION: Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.

Amorphous selenium inhibits oxidative stress injury of neurons in vascular dementia rats by activating NMDAR pathway.

Vascular dementia (VD) is one of the most common causes of dementia, taking account for about 20% of all cases. Although studies have found that selenium supplementation can improve the cognitive ability of Alzheimer's patients, there is currently no research on the cognitive impairment caused by VD. This study aimed to investigate the role and mechanism of Amorphous selenium nanodots (A SeNDs) in the prevention of VD. The bilateral common carotid artery occlusion (BCCAO) method was used to establish a VD model. The neuroprotective effect of A SeNDs was evaluated by Morris water maze, Transcranial Doppler TCD, hematoxylin-eosin (HE) staining, Neuron-specific nuclear protein (Neu N) staining and Golgi staining. Detect the expression levels of oxidative stress and Calcium-calmodulin dependent protein kinase II (CaMK II), N-methyl-D-aspartate receptor subunit NR2A, and postsynaptic dense protein 95 (PSD95). Finally, measure the concentration of calcium ions in neuronal cells. The results showed that A SeNDs could significantly improve the learning and memory ability of VD rats, restore the posterior arterial blood flow of the brain, improve the neuronal morphology and dendritic remodeling of pyramidal cells in hippocampal CA1 area, reduce the level of oxidative stress in VD rats, increase the expression of NR2A, PSD95, CaMK II proteins and reduce intracellular calcium ion concentration, but the addition of selective NR2A antagonist NVP-AAMO77 eliminated these benefits. It suggests that A SeNDs may improve cognitive dysfunction in vascular dementia rats by regulating the NMDAR pathway.

A novel transcription factor SIPA1: identification and verification in triple-negative breast cancer.

Transcription factors (TFs) regulate the expression of genes responsible for cell growth, differentiation, and responses to environmental factors. In this study, we demonstrated that signal-induced proliferation-associated 1 (SIPA1), known as a Rap-GTPase-activating protein, bound DNA and served as a TF. Importin ß1 was found to interact with SIPA1 upon fibronectin treatment. A TGAGTCAB motif was recognized and bound by DNA-binding region (DBR) of SIPA1, which was confirmed by electrophoretic mobility shift assay. SIPA1 regulated the transcription of multiple genes responsible for signal transduction, DNA synthesis, cell adhesion, cell migration, and so on. Transcription of fibronectin 1, which is crucial for cell junction and migration of triple-negative breast cancer (TNBC) cells, was regulated by SIPA1 in a DBR-dependent manner both in vivo and in vitro. Furthermore, single-cell transcriptome sequencing analysis of specimens from a metastatic TNBC patient revealed that SIPA1 was highly expressed in metastatic TNBC. Hence, this study demonstrated that SIPA1 served as a TF, promoting TNBC migration, invasion, and metastasis.

Perillaldehyde improves diabetic cardiomyopathy by upregulating miR-133a-3p to regulate GSK-3ß.

Diabetic cardiomyopathy (DCM) is part of the most important causes of death from cardiovascular disease. Perillaldehyde (PAE), a major component of the herb perilla, has been shown to ameliorate doxorubicin-induced cardiotoxicity, but it is unclear whether PAE exerts beneficial effects on DCM. Exploring the potential molecular mechanisms of PAE for the treatment of DCM through network pharmacology and molecular docking. The SD rat type 1 diabetes model was established by a single intraperitoneal injection of streptozotocin (60 mg/kg), the cardiac function indexes of each group were detected by echocardiography; the morphological changes, apoptosis, protein expression of P-GSK-3ß (S9), collagen I (Col-Ⅰ), collagen III (Col-Ⅲ) and alpha-smooth muscle actin (α-SMA), and miR-133a-3p expression levels were detected. An DCM model of H9c2 cells was established in vitro and transfected with Mimic and Inhibitor of miR-133a-3p. The results showed that PAE ameliorated cardiac dysfunction, reduced fasting glucose and cardiac weight index, and improved myocardial injury and apoptosis in DCM rats. It reduced high glucose-induced apoptosis, promoted migration and improved mitochondrial division injury in H9c2 cells. PAE decreased P-GSK-3ß (S9), Col-Ⅰ, Col-Ⅲ and α-SMA protein expression and upregulated miR-133a-3p expression levels. After miR-133a-3p Inhibitor treatment, the expression of P-GSK-3ß (S9) and α-SMA expression were significantly increased; after miR-133a-3p Mimic treatment, the expression of P-GSK-3ß (S9) and α-SMA decreased significantly in H9c2 cells. It suggests that the mechanism of action of PAE to improve DCM may be related to the upregulation of miR-133a-3p and inhibition of P-GSK-3ß expression.

Rh(III)-Catalyzed C-H Annulation of N-Nitrosoanilines with Iodonium Ylides for the Synthesis of N-Alkyl Indoles.

A novel protocol for synthesizing N-alkyl indoles from readily available N-nitrosoanilines and iodonium ylides through the rhodium(III)-catalyzed C-H bond activation/intramolecular cyclization reaction has been described. This strategy employs nitroso as a traceless directing group. The transformation features powerful reactivity, tolerates various functional groups, and proceeds with moderate yields under mild reaction conditions, providing a straightforward approach to access structurally diverse and valuable N-alkyl indole derivatives.

Case Report of a Successfully Treated Scopulariopsis Infection in a Bilateral Lung Transplant Recipient.

Scopulariopsis is a species of Aspergillus from the Microascaceae family. It has rarely been reported as a cause of human-borne infection. Here, we describe a 40-year-old female patient who had an invasive pulmonary Scopulariopsisinfection following bilateral lung transplant. During her routine follow-up posttransplant, new nodules were found on chest computed tomography imaging, bronchoalveolar lavage fluid cultures grew filamentous fungi, and lung biopsy was positive for Scopulariopsis. The patient had described a generalized weakness and fatigue for several weeks without cough or chest-related symptoms. After the patient received antifungal treatment, the nodules gradually disappeared, and she improved with good tolerance and without any adverse events. This was a rare case of proven invasive pulmonary Scopulariopsis infection in a lung transplant recipient that caused local disease and systemic infection, which we further analyzed by conducting a literature review. Ourreport can increase the current understanding pertaining to the treatment of a rare and lethal fungal opportunistic infection in immunocompromised humans.

Rapid and ratiometric fluorescent detection of hypochlorite by glutathione functionalized molybdenum disulfide quantum dots.

We proposed a rapid and ratiometric fluorescent detection method for hypochlorite by glutathione functionalized molybdenum disulfide quantum dots (G-MoS2 QDs). The G-MoS2 QDs were obtained through a hydrothermal method and the maximum fluorescence intensity was obtained at 430 nm under excitation of 360 nm. The fluorescence of G-MoS2 QDs at 430 nm can be weakened by curcumin through the inner filter effect, meanwhile the fluorescence of curcumin at 540 nm appeared. Hypochlorite can fast oxidize curcumin and weaken the inner filter effect, thus the fluorescence of curcumin at 540 nm decreased and the fluorescence of G-MoS2 QDs at 430 nm increased. This process takes only 30 s at room temperature. This is the rationale behind our rapid ratiometric fluorescent detection model for hypochlorite. Two linear detection ranges for hypochlorite are obtained with concentration from 1 to 20 µM and 20 to 30 µM, the limit of detection (LOD) was 11.5 nM. The standard spike recovery tests on milk and tap water samples showed satisfactory results, which extended the application of G-MoS2 QDs in the field of ratiometric fluorescence detection assays.