Constructing Metal-Organic Framework Films with Adjustable Electronic Properties on Hematite Photoanode for Boosting Photogenerated Carrier Transport.

Hematite (α-Fe2O3) has become a research hotspot in the field of photoelectrochemical water splitting (PEC-WS), but the low photogenerated carrier separation efficiency limits further application. The electronic structure regulation, such as element doping and organic functional groups with different electrical properties, is applied to alleviate the problems of poor electrical conductivity, interface defects, and band mismatch. Herein, α-Fe2O3 photoanodes are modified to regulate their electric structures and improve photogenerated carrier transport by the bimetallic metal-organic frameworks (MOFs), which are constructed with Fe/Ni and terephthalate (BDC) with 2-substitution of different organic functional groups (─H, ─Br, ─NO2 and ─NH2). The α-Fe2O3 photoanode loaded with FeNi-NH2BDC MOF catalyst exhibits the optimal photocurrent density (2 mA cm-2) at 1.23 VRHE, which is 2.33 times that of the pure α-Fe2O3 photoanode. The detailed PEC analyses demonstrate that the bimetallic synergistic effect between Fe and Ni can improve the conductivity and inhibit the photogenerated carrier recombination of α-Fe2O3 photoanodes. The ─NH2 group as an electron-donor group can effectively regulate the electron distribution and band structure of α-Fe2O3 photoanodes to prolong the lifetime of photogenerated holes, which facilitates photogenerated carrier transport and further enhances the PEC-WS performance of α-Fe2O3 photoanode.

WS2 Nanotube Transistor for Photodetection and Optoelectronic Memory Applications.

Nanotube and nanowire transistors hold great promises for future electronic and optoelectronic devices owing to their downscaling possibilities. In this work, a single multi-walled tungsten disulfide (WS2) nanotube is utilized as the channel of a back-gated field-effect transistor. The device exhibits a p-type behavior in ambient conditions, with a hole mobility µp ≈  1.4 cm2V-1s-1 and a subthreshold swing SS ≈ 10 V dec-1. Current-voltage characterization at different temperatures reveals that the device presents two slightly different asymmetric Schottky barriers at drain and source contacts. Self-powered photoconduction driven by the photovoltaic effect is demonstrated, and a photoresponsivity R ≈ 10 mAW-1 at 2 V drain bias and room temperature. Moreover, the transistor is tested for data storage applications. A two-state memory is reported, where positive and negative gate pulses drive the switching between two different current states, separated by a window of 130%. Finally, gate and light pulses are combined to demonstrate an optoelectronic memory with four well-separated states. The results herein presented are promising for data storage, Boolean logic, and neural network applications.

PbBeB2O5: A High-Performance Ultraviolet Nonlinear-Optical Crystal with Functional [BeB2O8]8- Group.

High-performance nonlinear-optical (NLO) crystals need to simultaneously meet multiple basic and conflicting performance requirements. Here, by using a partial chemical substitution strategy, the first noncentrosymmetric (NCS) PbBeB2O5 crystal with a BeB2O8 group was synthesized, exhibiting a two-dimensional [BeB2O5]∞ layer constructed by interconnecting BeB2O8 groups and bridged PbO4 with an active lone pair. The crystal shows a promising UV NLO functional feature, including a strong SHG effect of 3.5 × KDP (KH2PO4), large birefringence realizing phase matchability in the whole transparency region from 246 to 2500 nm, a short UV absorption edge of 246 nm, and single-crystal easy growth. Remarkably, theoretical studies reveal that the BeB2O8 group has high nonlinear activity, which could stimulate the discovery of a series of excellent NLO beryllium borates.

Clinicopathological characteristics and survival analysis of different molecular subtypes of breast invasive ductal carcinoma achieving pathological complete response through neoadjuvant chemotherapy.

BACKGROUND: To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. RESULTS: This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan-Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05). CONCLUSIONS: Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.

Correlation between gene polymorphism and adverse reactions of high-dose methotrexate in osteosarcoma patients: a systematic review and meta-analysis.

OBJECTIVE: We aimed to provide a reference based on evidence for an individualized clinical medication of high-dose methotrexate (HD-MTX) in osteosarcoma patients by evaluating the effect of gene polymorphism on adverse reactions of HD-MTX usage. METHODS: Several databases were combed for research on the association between gene polymorphisms and adverse reactions to HD-MTX up to January 2023. A meta-analysis and/or descriptive analysis on the incidence of HD-MTX-related adverse reactions were conducted by using clinical studies meeting inclusion criteria. RESULTS: Twelve studies involving 889 patients were included. There were 8, 6, 5, and 4 studies related to MTHFR C677T, MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphisms, respectively. The results of the meta-analysis showed that the MTHFR C677T polymorphism was associated with G3-4 hepatotoxicity, G3-4 nephrotoxicity, G3-4 gastrointestinal toxicity, and G3-4 mucositis under the recessive genetic model (MM vs. Mm/mm). Limited research showed that MTHFR C677T was associated with G3-4 nephrotoxicity in the allelic genetic model (M vs. m). MTHFR A1298C polymorphism was associated with a decreased risk of adverse reactions to HD-MTX usage, without statistical significance. This review's descriptive analysis showed no significant correlation between the RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions of HD-MTX. CONCLUSION: The MTHFR C677T mutation may enhance the risk of HD-MTX adverse reactions in osteosarcoma patients. Existing studies have not found a significant correlation between the MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions caused by HD-MTX. Lastly, this conclusion was limited because of few studies.

Co-exposure of microcystin-LR and nitrite induced kidney injury through TLR4/NLRP3/GSDMD-mediated pyroptosis.

The degradation of cyanobacterial blooms releases hazardous contaminants such as microcystin-LR (MC-LR) and nitrite, which may collectively exert toxicity on various bodily systems. To evaluate their individual and combined toxicity in the kidney, mice were subjected to different concentrations of MC-LR and/or nitrite over a 6-month period in this study. The results revealed that combined exposure to MC-LR and nitrite exacerbated renal pathological alterations and dysfunction compared to exposure to either compound alone. Specifically, the protein and mRNA expression of kidney injury biomarkers, such as kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), were notably increased in combined exposure group. Concurrently, co-exposure to MC-LR and nitrite remarkedly upregulated levels of proinflammatory cytokines TNF-α, IL-6 and IL-1ß, while decreasing the anti-inflammatory cytokine IL-10. Notably, MC-LR and nitrite exhibited synergistic effects on the upregulation of renal IL-1ß levels. Moreover, MC-LR combined with nitrite not only elevated mRNA levels of proinflammatory cytokines but also increased protein levels of pyroptosis biomarkers such as IL-1ß, Gasdermin D (GSDMD), and Cleaved-GSDMD. Mechanistic investigations revealed that co-exposure to MC-LR and nitrite promoted pyroptosis both in vivo and in vitro, possibly through the activation of the TLR4/NLRP3/GSDMD pathway. Pretreatment with TLR4 inhibitor and NLRP3 inhibitor effectively suppressed pyroptosis induced by the co-exposure of these two toxins in HEK293T cells. These findings provide compelling evidence that MC-LR combined with nitrite synergistically induces pyroptosis in the kidney by activating the TLR4/NLRP3/GSDMD pathway. Overall, this study significantly enhances our comprehension of how environmental toxins interact and induce harm to the kidneys, offering promising avenues for identifying therapeutic targets to alleviate their toxic effects on renal health.

Unraveling the pesticide-diabetes connection: A case-cohort study integrating Mendelian randomization analysis with a focus on physical activity's mitigating effect.

BACKGROUND AND AIMS: There is no evidence on the longitudinal and causal associations between multiple pesticides and the incidence of type 2 diabetes mellitus (T2DM) in the Chinese rural population, and whether physical activity (PA) modified these associations remains unclear. Here, we aimed to investigate the longitudinal and causal associations between pesticides mixture and T2DM, and determine whether PA modified these associations. METHODS: A total of 925 subjects with normal glucose and 925 subjects with impaired fasting glucose (IFG) were enrolled in this case-cohort study. A total of 51 targeted pesticides were quantified at baseline. Logistic regression, quantile g-computation, and Bayesian kernel machine regression (BKMR) were used to assess the individual and combined effects of pesticides on IFG and T2DM. Mendelian randomization (MR) analysis was employed to obtain the causal association between pesticides and T2DM. RESULTS: After 3-year follow-up, one-unit increment in ln-isofenphos, ln-malathion, and ln-deltamethrin were associated with an increase conversion of IFG to T2DM (FDR-P<0.05). One quartile increment in organochlorine pesticides (OCPs), organophosphorus pesticides (OPs), herbicides and pyrethroids mixtures were related to a higher incidence of T2DM among IFG patients (P<0.05). The BKMR results showed a positive trend between exposure to pesticides mixture and T2DM. The MR analysis indicated a positive association between exposure to pesticides and T2DM risk (P<0.05). No any significant association was found between pesticides and IFG. In addition, compared to subjects with high levels of PA, those with low levels of PA were related to increased risk of T2DM with the increased levels of pesticides among IFG patients. CONCLUSIONS: Individual and combined exposure to pesticides increased the incidence of T2DM among IFG patients. MR analysis further supported the causal association of pesticides exposure with T2DM risk. Our study furtherly indicated that high levels of PA attenuated the diabetogenic effect of pesticides exposure.

A novel configuration for the fixation of intra-articular C2.3 distal humerus fractures with the potential for minimally invasive surgery: a biomechanical evaluation and finite element analysis.

BACKGROUND: Distal humerus fractures are a challenge to treat, and the current standard of care, open reduction internal fixation with a double-plate, has a high rate of complications. We proposed a novel internal fixation configuration, lateral intramedullary nail and medial plate (LINMP) and verified its rigidity through biomechanical tests and finite element analysis. METHODS: The study involved biomechanical testing of 30 synthetic humerus models to compare 2 different fixation systems for an AO 13C-2.3 type fracture. The orthogonal double-plate (ODP) group and the LINMP group were compared through biomechanical testing to measure stiffness and failure load fewer than 3 working conditions. Based on the results, we optimized the intramedullary nail by eliminating the holes at the distal end of the nail and incorporating a 2-hole external locking plate. The Finite element analysis was also conducted to further compare the modified LINMP configuration with the previous 2 fixation configurations. RESULTS: In biomechanical tests, the ODP group exhibited lower stiffness under bending and compression forces compared to the LINMP group, but higher stiffness and failure loads under torsion force. In finite element analysis, the modified LINMP reduces the maximum stress of the fixation structure without significantly reducing the stiffness under bending stress and axial compression conditions. In torsion stress conditions, the modified LINMP enhances both the maximum stress and the stiffness, although it remains marginally inferior to the ODP structure. CONCLUSION: Our study demonstrates that the innovative LINMP presents comparable or slightly superior concerning bending and axial loading compared to orthogonal double-plate osteosynthesis for distal humeral intra-articular fractures, which might become a minimally invasive option for these fractures.

Global left ventricular myocardial work: A novel method to assess left ventricular myocardial function and predict major adverse cardiovascular events in maintenance hemodialysis patients.

BACKGROUND: The application value of myocardial work (MW) in evaluating myocardial function and predicting major adverse cardiovascular events (MACE) in maintenance hemodialysis (MHD) patients has not been fully explored. PURPOSE: Comparing noninvasive MW parameters between MHD patients and healthy controls, and further determining its value in predicting MACE in MHD patients. METHODS: A prospective single-institution study included 92 MHD patients without prior cardiovascular disease and 40 age- and sex-matched healthy controls. Conventional echocardiographic data, global longitudinal strain (GLS), and MW parameters (global work index [GWI], global constructive work [GCW], global work efficiency [GWE], global wasted work [GWW]) were derived and compared between MHD and the control. Logistic regression was used to determine the predictive value of these parameters for MACE. The receiver operating characteristic curve was utilized to compare the predictive differences of MACE between GWE and GLS. RESULTS: Compared with healthy individuals, MHD patients had significantly reduced GWE, GLS and elevated LVMI, GWW (all p < 0.001), while there was no significant difference in left ventricular ejection fraction. Twenty eight (30%) MHD patients experienced MACE. Two nested models adding GWE and GLS, respectively, showed that age (p < 0.005), GWE (p = 0.034), and GLS (p = 0.014) were independent predictors of MACE. The AUC derived from GWE for predicting MACE was significantly higher than that derived from GLS (0.836 vs. 0.743, p = 0.039). CONCLUSIONS: Myocardial work is a novel tool for assessing left ventricular myocardial performance in MHD patients. GWE is an independent predictor of MACE.

An optimization by response surface methodology for the enhanced production of rMBSP from Pichia pastoris and study of its application.

Background: Recombinant myofibril-bound serine proteinase (rMBSP) was successfully expressed in Pichia pastoris GS115 in our laboratory. However, low production of rMBSP in shake flask constraints further exploration of properties.Methods: A 5-L high cell density fermentation was performed and the fermentation medium was optimized. Response surface methodology (RSM) was used to optimize the culture condition through modeling three selected parameter.Results: Under the optimized culture medium (LBSM, 1% yeast powder and 1% peptone) and culture conditions (induction pH 5.5, temperature 29 °C, time 40 h), the yield of rMBSP was 420 mg/L in a 5-L fermenter, which was a 6-fold increase over thar, expressed in flask cultivation. The desired enzyme was purified by two-step, which yielded a 33.7% recovery of a product that had over 85% purity. The activity of purified rMBSP was significantly inhibited by Ca2+, Mg2+, SDS, guanidine hydrochloeide, acetone, isopropanol, chloroform, n-hexane and n-heptane. Enzymatic analysis revealed a Km of 2.89 ± 0.09 µM and a Vmax of 14.20 ± 0.12 nM•min-1 for rMBSP. LC-MS/MS analysis demonstrated the specific cleavage of bovine serum albumin by rMPSP.Conclusion: These findings suggest that rMPSP has potential as a valuable enzyme for protein science research.

SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD), effectively shrinks tumors both in intracranial and subcutaneous ER + breast cancer models.

BACKGROUND: Targeted estrogen receptor degradation has been approved to effectively treat ER + breast cancers. Due to the poor bioavailability of fulvestrant, the first generation of SERD, many efforts were made to develop oral SERDs. With the approval of Elacestrant, oral SERDs demonstrated superior efficacy than fulvestrant. However, due to the poor ability of known SERDs to penetrate the blood-brain barrier (BBB), breast cancer patients with brain metastasis cannot benefit from clinical SERDs. METHODS: The ER inhibitory effects were evaluated on ERα protein degradation, and target genes downregulation. And anti-proliferation activities were further determined in a panel of ER + breast cancer cell lines. The subcutaneous and intracranial ER + tumor models were used to evaluate the efficacy of anti-tumor effects. Brain penetrability was determined in multiple animal species. RESULTS: SCR-6852 is a novel SERD and currently is under early clinical evaluation. In vitro studies demonstrated that it strongly induced both wildtype and mutant ERα degradation. It potently inhibited cell proliferation in a panel of ER + breast cancer cell lines, including the cell lines containing ESR1 mutations (Y537 and D538). Furthermore, SCR-6852 exhibited pure antagonistic activities on the ERɑ signal axis identified both in vitro and in vivo. Oral administration of SCR-6852 at 10 mg/kg resulted in tumor shrinkage which was superior to Fulvestrant at 250 mg/kg, notably, in the intracranial tumor model, SCR-6852 effectively inhibited tumor growth and significantly prolonged mice survival, which correlated well with the high exposure in brains. In addition to mice, SCR-6852 also exhibited high brain penetrability in rats and dogs. CONCLUSIONS: SCR-6852 is a novel SERD with high potency in inducing ERα protein degradation and pure antagonistic activity on ERɑ signaling in vitro and in vivo. Due to the high brain penetrability, SCR-6852 could be used to treat breast patients with brain metastasis.

AgMYB5, an MYB transcription factor from celery, enhanced ß-carotene synthesis and promoted drought tolerance in transgenic Arabidopsis.

BACKGROUND: Water shortage caused by global warming seriously affects the yield and quality of vegetable crops. ß-carotene, the lipid-soluble natural product with important pharmacological value, is abundant in celery. Transcription factor MYB family extensively disperses in plants and plays regulatory roles in carotenoid metabolism and water scarcity response. RESULTS: Here, the AgMYB5 gene encoding 196 amino acids was amplified from celery cv. 'Jinnanshiqin'. In celery, the expression of AgMYB5 exhibited transactivation activity, tissue specificity, and drought-condition responsiveness. Further analysis proved that ectopic expression of AgMYB5 increased ß-carotene content and promoted drought tolerance in transgenic Arabidopsis thaliana. Moreover, AgMYB5 expression promoted ß-carotene biosynthesis by triggering the expression of AtCRTISO and AtLCYB, which in turn increased antioxidant enzyme activities, and led to the decreased contents of H2O2 and MDA, and the inhibition of O2- generation. Meanwhile, ß-carotene accumulation promoted endogenous ABA biosynthesis of transgenic Arabidopsis, which resulted in ABA-induced stomatal closing and delayed water loss. In addition, ectopic expression of AgMYB5 increased expression levels of AtERD1, AtP5CS1, AtRD22, and AtRD29. CONCLUSIONS: The findings indicated that AgMYB5 up-regulated ß-carotene biosynthesis and drought tolerance of Arabidopsis.

Temperature-mediated microbial carbon utilization in China's lakes.

Microbes play an important role in aquatic carbon cycling but we have a limited understanding of their functional responses to changes in temperature across large geographic areas. Here, we explored how microbial communities utilized different carbon substrates and the underlying ecological mechanisms along a space-for-time substitution temperature gradient of future climate change. The gradient included 47 lakes from five major lake regions in China spanning a difference of nearly 15°C in mean annual temperatures (MAT). Our results indicated that lakes from warmer regions generally had lower values of variables related to carbon concentrations and greater carbon utilization than those from colder regions. The greater utilization of carbon substrates under higher temperatures could be attributed to changes in bacterial community composition, with a greater abundance of Cyanobacteria and Actinobacteriota and less Proteobacteria in warmer lake regions. We also found that the core species in microbial networks changed with increasing temperature, from Hydrogenophaga and Rhodobacteraceae, which inhibited the utilization of amino acids and carbohydrates, to the CL500-29-marine-group, which promoted the utilization of all almost carbon substrates. Overall, our findings suggest that temperature can mediate aquatic carbon utilization by changing the interactions between bacteria and individual carbon substrates, and the discovery of core species that affect carbon utilization provides insight into potential carbon sequestration within inland water bodies under future climate warming.

Ordered Assembly of DNA on Topological Insulator Bi2Se3 and Octadecylamine for a Sensitive Biosensor.

Controlling the assembly of DNA in order on a suitable electrode surface is of great significance for biosensors and disease diagnosis, but it is full of challenges. In this work, we creatively assembled DNA on the surface of octadecylamine (ODA)-modified topological insulator (Tls) Bi2Se3 and developed an electrochemical biosensor to detect biomarker DNA of coronavirus disease 2019 (COVID-19). A high-quality Bi2Se3 sheet was obtained from a single crystal synthesized in our lab. A uniform ODA layer was coated in argon by chemical vapor deposition (CVD). We observed and analyzed the assembly and mechanism of single-strand DNA (ssDNA) and double-strand DNA (dsDNA) on the Bi2Se3 surface through atomic force microscopy (AFM) and molecular dynamics (MD) simulations. The electrochemical signal revealed that the biosensor based on the DNA/ODA/Bi2Se3 electrode has a wide linear detection range from 1.0 × 10-12 to 1.0 × 10-8 M, with the limit of detection as low as 5 × 10-13 M. Bi2Se3 has robust surface states and improves the electrochemical signal-to-noise ratio, while the uniform ODA layer guides high-density ordered DNA, enhancing the sensitivity of the biosensor. Our work demonstrates that the ordered DNA/ODA/Bi2Se3 electrode surface has great application potential in the field of biosensing and disease diagnosis.

Photomodulation of Proton Conductivity by Nitro-Nitroso Transformation in a Metal-Organic Framework.

The design of a highly and photomodulated proton conductor is important for advanced potential applications in chemical sensors and bioionic functions. In this work, a metal-organic framework (MOF; Gd-NO2) with high proton conductivity is synthesized with a photosensitive ligand of 5-nitroisophthalic acid (BDC-NO2), and it provides remote-control photomodulated proton-conducting behavior. The proton conduction of Gd-NO2 reaches 3.66 × 10-2 S cm-1 at 98% relative humidity (RH) and 25 °C, while it decreases by ∼400 times after irradiation with a 355 nm laser. The newly generated and disappearing FT-IR characteristic peaks reveal that this photomodulated process is realized by the photoinduced transformation from BDC-NO2 to 5-nitroso-isophthalic acid (BDC-NO). According to density functional theory, the smaller electronegativity of the -NO group, the longer distance of the hydrogen bond between BDC-NO and H2O molecules, and the lower water adsorption energy of BDC-NO indicate that the irradiated sample possesses a poorer hydrophilicity and has difficulty forming rich hydrogen-bonded networks, which results in the remarkable decrease of proton conductivity.

miR-222-3p-containing macrophage-derived extracellular vesicles confer gemcitabine resistance via TSC1-mediated mTOR/AKT/PI3K pathway in pancreatic cancer.

Gemcitabine resistance limits the efficacy of chemotherapy and maintains a challenge for treatment outcomes. Therefore, we aimed to clarify the downstream mechanisms underlying the role of miR-222-3p delivered by M2 macrophage-derived extracellular vesicles (M2 MDEs) in the chemoresistance of pancreatic cancer (PCa). We separated the mouse macrophages and polarized them to M2 phenotypes, from which the EVs were derived. miR-222-3p was highly expressed in M2 MDEs. M2 MDEs were internalized by PCa cells. miR-222-3p overexpressing M2 MDEs were treated with gemcitabine and co-cultured with PCa cells for in vitro experiments. Co-culture with M2 MDEs enriched with miR-222-3p suppressed the sensitivity to gemcitabine, accompanied by diminished apoptosis and promoted proliferation. Furthermore, the M2 MDEs and PCa cells were injected to mice with gemcitabine exposure for in vivo substantiation. The delivery of miR-222-3p inhibitor by M2 MDEs suppressed tumor growth and elevated sensitivity of cancer cells to gemcitabine. Moreover, miR-222-3p was indicated to target and suppress TSC1 expression, while miR-222-3p activated the PI3K/AKT/mTOR pathway. Together, miR-222-3p-containing M2 MDEs enhance chemoresistance in PCa through TSC1 inhibition and activation of the PI3K/AKT/mTOR pathway.

Insight into the interface engineering between methylammonium lead halide perovskites and gallium oxide: a first-principles approach.

Interface engineering of the organo-lead halide perovskite devices has shown the potential to improve their efficiency and stability. In this study, the atomic, electronic, optical and transport characteristics of MAPbI3/Ga2O3 and MAPbCl3/Ga2O3 interfaces were investigated by using first-principles calculations. Eight different interfacial models were established and the interfacial properties were discussed. The results show that the PbI/O configuration exhibits the largest bonding strength out of all eight interfacial configurations. Owing to the larger interfacial interaction, the charge transfer at the PbI/O interface is significantly more than that at the other interfaces. The analysis of absorption spectra indicates that the Ga-terminated perovskite/Ga2O3 heterostructures are expected to have great potential for efficient optoelectronic applications. The analysis of transmission spectra shows that the MA/O configurations with more transmission peaks near the Fermi level exhibit lower resistance compared to others. The results of our study could help understand the interfacial engineering mechanism between perovskite and Ga2O3.

Targeting Glutamine Metabolism as an Attractive Therapeutic Strategy for Acute Myeloid Leukemia.

OPINION STATEMENT: Relapse after chemotherapy and hematopoietic stem cell transplantation leads to adverse prognosis for acute myeloid leukemia (AML) patients. As a "conditionally essential amino acid," glutamine contributes to the growth and proliferation of AML cells. Glutamine-target strategies as new treatment approaches have been widely explored in AML treatment to improve outcome. Glutamine-target strategies including depletion of systemic glutamine and application of glutamine uptake inhibitors, glutamine antagonists/analogues, and glutaminase inhibitors. Because glutamine metabolism involved in multiple pathways in cells and each pathway of glutamine metabolism has many regulatory factors, therefore, AML therapy targeting glutamine metabolism should focus on how to inhibit multiple metabolic pathways without affecting normal cells and host immune to achieve effective treatment for AML.

Secondary leaflet tethering in patients with severe degenerative mitral regurgitation and its association with the severity of mitral regurgitation.

BACKGROUND: The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. METHODS: We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 21 healthy controls. MVPt+ group was defined as tenting volume index (TVi) > .7 mL/m2 . The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. RESULTS: Of the 94 patients with MVP and significant MR, 31 patients showed a TVi > .7 mL/m2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi were independently associated with 3D VCA. 3D VCA, annular area index, and plasma levels of NT-proBNP were independently correlated with the severity of leaflet tethering. ROC curve revealed that a 3D VCA ≥ .55 cm2 is the optimal cutoff point to predict MVPt+ phenotype. CONCLUSIONS: Secondary leaflet tethering is a significant mechanism behind severe degenerative MR, resulting in an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics.

Hawthorn fruit extract protect against MC-LR-induced hepatotoxicity by attenuating oxidative stress and apoptosis.

Microcystins (MCs) is a class of cyclic heptapeptide compounds with biological activity. There is no effective treatment for liver injury caused by MCs. Hawthorn is a medicinal and edible plant traditional Chinese medicine with hypolipidemic, reducing inflammation and oxidative stress in the liver. This study discussed the protective effect of hawthorn fruit extract (HFE) on liver damage caused by MC-LR and the underlying molecular mechanism. After MC-LR exposure, pathological changes were observed and hepatic activity of ALT, AST and ALP were increased obviously, but they were remarkably restored with HFE administration. In addition, MC-LR could significantly reduce SOD activity and increase MDA content. Importantly, MC-LR treatment resulted in mitochondrial membrane potential decreased, and Cytochrome C release, eventually leading to cell apoptosis rate increase. HFE pretreatment could significantly alleviate the above abnormal phenomena. To examine the mechanism of protection, the expression of critical molecules in the mitochondrial apoptosis pathway was examined. The levels of Bcl-2 was inhibited, and the levels of Bax, Caspase-9, Cleaved Caspase-9, and Cleaved caspase-3 were upregulated after MC-LR treatment. HFE reduced MC-LR-induced apoptosis via reversing the expression of key proteins and genes in the mitochondrial apoptotic pathway. Hence, HFE could alleviate MC-LR induced hepatotoxicity by reducing oxidative stress and apoptosis.