Efficacy of scleral buckling for the treatment of rhegmatogenous retinal detachment using a novel foldable capsular buckle.

AIM: To evaluate the effectiveness and safety of scleral buckling for the treatment of rhegmatogenous retinal detachment (RRD) using a novel foldable capsular buckle (FCB). METHODS: This was a series of case observation studies. Eighteen patients (18 eyes) who visited our ophthalmology department between August 2020 and August 2022 and were treated for RRD with scleral buckling using FCB were included. The procedure was similar to conventional scleral buckling, while a balloon-like FCB was placed onto the retinal break with balanced salt solution filling for a broad, external indentation instead of the silicone buckle. The retinal reattachment rate, best corrected visual acuity (BCVA), intraocular pressure (IOP), refractive dioptre and astigmatism degree, and complications were evaluated and recorded. RESULTS: There were 7 males and 11 females aged 19-58y. The average time course of RRD was 12d, ranging from 7-20d. The retinal break was located in the superior quadrants in 8 eyes and in the inferior quadrants in 10 eyes, with macula-off detachments in 12 eyes. The patients were followed-up for at least 6mo. The final retinal reattachment rate was 100%. The BCVA was significantly improved compared with the baseline (P<0.05). There was no significant change in refractive dioptre or astigmatism degree at each follow-up (all P>0.05). Three patients had transiently high IOPs within one week after surgery. Mild diplopia occurred in 5 patients after surgery and then disappeared after the balloon fluid was removed. CONCLUSION: The success rate of FCB scleral buckling for RRD is satisfactory. This procedure can be expected to be applied in new, uncomplicated cases of RRD.

Antimicrobial resistance and population genomics of emerging multidrug-resistant Salmonella 4,[5],12:i:- in Guangdong, China.

Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.

The Influence of Al and Nb on the Low Oxygen Pressure Pre-Oxidation Behavior of Fe-35Ni-20Cr-xAl-yNb Alloys at 1000 °C.

To investigate the impact of Al and Nb elements on the formation of a protective oxide layer on the surface of Fe-35Ni-20Cr-xAl-yNb (x = 0, 2, 4, 6 wt.%; y = 0, 1, 2 wt.%) alloys, their oxidation behavior was examined at 1000 °C, 10-17 atm. and 10-25 atm. oxygen pressure, and the oxidation mechanism was analyzed by Factsage and Pandat calculations. Enhancing the Al content at 10-17 atm. inhibited the generation of FeCr2O4 on the alloy surface and increased the Al content in the M2O3 layer. When the Al content exceeded 6 wt.%, the oxide film partially peeled off. It was found that the addition of Nb increased the activity of Cr and Al and decreased the activity of Ni and Fe and promoted the formation of Al2O3, and the appearance of Nb2O5 in the subsurface layer increased the density of the oxide film. In addition, under an oxygen pressure of 10-25 atm., the only protective layer on the surface of the alloy comprised of Al2O3. The experimental results demonstrated that the Fe-35Ni-20Cr-4Al-2Nb alloy generated a continuous and dense Al2O3 protective film, and the reduction in oxygen pressure and the addition of Nb elements were favorable for selective external oxidation of Al2O3.

Effects of joint screening for prostate, lung, colorectal, and ovarian cancer - results from a controlled trial.

Background: Although screening is widely used to reduce cancer burden, untargeted cancers are frequently missed after single cancer screening. Joint cancer screening is presumed as a more effective strategy to reduce overall cancer burden. Methods: Gender-specific screening effects on PLCO cancer incidence, PLCO cancer mortality, all-neoplasms mortality and all-cause mortality were evaluated, and meta-analyses based on gender-specific screening effects were conducted to achieve the pooled effects. The cut-off value of time-dependent receiver-operating-characteristic curve of 10-year combined PLCO cancer risk was used to reclassify participants into low- and high-risk subgroups. Further analyses were conducted to investigate screening effects stratified by risk groups and screening compliance. Results: After a median follow-up of 10.48 years for incidence and 16.85 years for mortality, a total of 5,506 PLCO cancer cases, 1,845 PLCO cancer deaths, 3,970 all-neoplasms deaths, and 14,221 all-cause deaths were documented in the screening arm, while 6,261, 2,417, 5,091, and 18,516 outcome-specific events in the control arm. Joint cancer screening did not significantly reduce PLCO cancer incidence, but significantly reduced male-specific PLCO cancer mortality (hazard ratio and 95% confidence intervals [HR(95%CIs)]: 0.88(0.82, 0.95)) and pooled mortality [0.89(0.84, 0.95)]. More importantly, joint cancer screening significantly reduced both gender-specific all-neoplasm mortality [0.91(0.86, 0.96) for males, 0.91(0.85, 0.98) for females, and 0.91(0.87, 0.95) for meta-analyses] and all-cause mortality [0.90(0.88, 0.93) for male, 0.88(0.85, 0.92) for female, and 0.89(0.87, 0.91) for meta-analyses]. Further analyses showed decreased risks of all-neoplasm mortality was observed with good compliance [0.72(0.67, 0.77) for male and 0.72(0.65, 0.80) for female] and increased risks with poor compliance [1.61(1.40, 1.85) for male and 1.30(1.13, 1.40) for female]. Conclusion: Joint cancer screening could be recommended as a potentially strategy to reduce the overall cancer burden. More compliance, more benefits. However, organizing a joint cancer screening not only requires more ingenious design, but also needs more attentions to the potential harms. Trial registration: NCT00002540 (Prostate), NCT01696968 (Lung), NCT01696981 (Colorectal), NCT01696994 (Ovarian).

A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues.

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.

CYP3A4 and CYP2C19 genetic polymorphisms and myricetin interaction on tofacitinib metabolism.

Tofacitinib can effectively improve the clinical symptoms of rheumatoid arthritis (RA) patients. In this current study, a recombinant human CYP2C19 and CYP3A4 system was operated to study the effects of recombinant variants on tofacitinib metabolism. Moreover, the interaction between tofacitinib and myricetin was analyzed in vitro. The levels of M9 (the main metabolite of tofacitinib) was detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The findings revealed that 11 variants showed significant changes in the levels of M9 compared to CYP3A4.1, while the other variants didn't reveal any remarkable significances. Compared with CYP2C19.1, 11 variants showed increases in the levels of M9, and 10 variants showed decreases. Additionally, it was demonstrated in vitro that the inhibition of tofacitinib by myricetin was a non-competitive type in rat liver microsomes (RLM) and human liver microsomes (HLM). However, the inhibitory mechanism was a competitive type in CYP3A4.18, and mixed type in CYP3A4.1 and .28, respectively. The data demonstrated that gene polymorphisms and myricetin had significant effects on the metabolism of tofacitinib, contributing to important clinical data for the precise use.

Pathophysiology and transcriptomic responses of Pinus armandii defenses to ophiostomatoid fungi.

Pinus armandii is an ecologically and economically important evergreen tree species native to western China. Dendroctonus armandi and pathogenic ophiostomatoid fungi pose substantial threats to P. armandii. With the interplay between species, the defense mechanisms of P. armandii have evolved to withstand external biotic stressors. However, the interactions between P. armandii and pathogenic ophiostomatoid fungal species/strains remain poorly understood. We aimed to analyze the pathophysiological and molecular changes in P. armandii following artificial inoculation with four ophiostomatoid species (Graphilbum parakesiyea, Leptographium qinlingense, Ophiostoma shennongense, and Ophiostoma sp. 1). The study revealed that L. qinlingense produced the longest necrotic lesions, and G. parakesiyea produced the shortest. All strains induced monoterpenoid release, and monoterpene levels of P. armandii were positively correlated with fungal virulence (R2 = 0.93, P < 0.01). Co-inoculation of two dominant highly (L. qinlingense) and weakly virulent (O. shennongense) pathogens reduced the pathogenicity of the highly virulent fungi. Transcriptomic analysis of P. armandii (LQ: L. qinlingense treatments, QS: co-inoculation treatments, and OS: O. shennongense treatments) showed that the expression pattern of differentially expressed genes (DEGs) between QS and OS was similar, but different from that of LQ. The DEGs (LQ vs. QS) involved in flavonoid biosynthesis and phenylpropanoid biosynthesis were downregulated. Notably, compared with LQ, QS significantly decreased the expression of host defense-related genes. This study provides a valuable theoretical basis for managing infestations of D. armandi and associated ophiostomatoid fungi.

Axillary lymph node metastasis in pure mucinous carcinoma of breast: clinicopathologic and ultrasonographic features.

BACKGROUND: The purpose of this research is to study the sonographic and clinicopathologic characteristics that associate with axillary lymph node metastasis (ALNM) for pure mucinous carcinoma of breast (PMBC). METHODS: A total of 176 patients diagnosed as PMBC after surgery were included. According to the status of axillary lymph nodes, all patients were classified into ALNM group (n = 15) and non-ALNM group (n = 161). The clinical factors (patient age, tumor size, location), molecular biomarkers (ER, PR, HER2 and Ki-67) and sonographic features (shape, orientation, margin, echo pattern, posterior acoustic pattern and vascularity) between two groups were analyzed to unclose the clinicopathologic and ultrasonographic characteristics in PMBC with ALNM. RESULTS: The incidence of axillary lymph node metastasis was 8.5% in this study. Tumors located in the outer side of the breast (upper outer quadrant and lower outer quadrant) were more likely to have lymphatic metastasis, and the difference between the two group was significantly (86.7% vs. 60.3%, P = 0.043). ALNM not associated with age (P = 0.437). Although tumor size not associated with ALNM(P = 0.418), the tumor size in ALNM group (32.3 ± 32.7 mm) was bigger than non-ALNM group (25.2 ± 12.8 mm). All the tumors expressed progesterone receptor (PR) positively, and 90% of all expressed estrogen receptor (ER) positively, human epidermal growth factor receptor 2 (HER2) were positive in two cases of non-ALNM group. Ki-67 high expression was observed in 36 tumors in our study (20.5%), and it was higher in ALNM group than non-ALNM group (33.3% vs. 19.3%), but the difference wasn't significantly (P = 0.338). CONCLUSIONS: Tumor location is a significant factor for ALNM in PMBC. Outer side location is more easily for ALNM. With the bigger size and/or Ki-67 higher expression status, the lymphatic metastasis seems more likely to present.

Per- and polyfluoroalkyl substances (PFAS) exposure in plasma and their blood-brain barrier transmission efficiency-A pilot study.

Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood-brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (RPFAS). This RPFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r2 = 0.94; p < 0.01) between RFOSA and Ki-67 (a molecular marker of glioma). However, a causal relationship between RFOSA and glioma incidence were not established in the present study. The present pilot study conducted the first examination of BBB transmission efficiency of PFAS from plasma to brain tissue and highlighted the importance of reducing and/or controlling exposure to PFAS.

Direct Photocatalytic Methane Oxidation to Formaldehyde by N Doping Co-Decorated Mixed Crystal TiO2.

In this paper, N-doped TiO2 mixed crystals are prepared via direct calcination of TiN for highly selective oxidation of CH4 to HCHO at room temperature. The structures of the prepared TiO2 samples are characterized to be N-doped TiO2 of anatase and rutile mixed crystals. The crystal structures of TiO2 samples are determined by XRD spectra and Raman spectra, while N doping is demonstrated by TEM mapping, ONH inorganic element analysis, and high-resolution XPS results. Significantly, the production rate of HCHO is as high as 23.5 mmol·g-1·h-1 with a selectivity over 90%. Mechanism studies reveal that H2O is the main oxygen source and acts through the formation of ·OH. DFT calculations indicate that the construction of a mixed crystal structure and N-doping modification mainly act by increasing the adsorption capacity of H2O. An efficient photocatalyst was prepared by us to convert CH4 to HCHO with high yield and selectivity, greatly promoting the development of the photocatalytic CH4 conversion study.

Extracellular Vesicles Derived from Neutrophils Accelerate Bone Regeneration by Promoting Osteogenic Differentiation of BMSCs.

The reconstruction of bone defects has been associated with severe challenges worldwide. Nowadays, bone marrow mesenchymal stem cell (BMSC)-based cell sheets have rendered this approach a promising way to facilitate osteogenic regeneration in vivo. Extracellular vesicles (EVs) play an essential role in intercellular communication and execution of various biological functions and are often employed as an ideal natural endogenous nanomedicine for restoring the structure and functions of damaged tissues. The perception of polymorphonuclear leukocytes (neutrophils, PMNs) as indiscriminate killer cells is gradually changing, with new evidence suggesting a role for these cells in tissue repair and regeneration, particularly in the context of bone healing. However, the role of EVs derived from PMNs (PMN-EVs) in bone regeneration remains largely unknown, with limited research being conducted on this aspect. In the current study, we investigated the effects of PMN-EVs on BMSCs and the underlying molecular mechanisms as well as the potential application of PMN-EVs in bone regeneration. Toward this end, BMSC-based cell sheets with integrated PMN-EVs (BS@PMN-EVs) were developed for bone defect regeneration. PMN-EVs were found to significantly enhance the proliferation and osteogenic differentiation of BMSCs in vitro. Furthermore, BS@PMN-EVs were found to significantly accelerate bone regeneration in vivo by enhancing the maturation of the newly formed bone in rat calvarial defects; this is likely attributable to the effect of PMN-EVs in promoting the expression of key osteogenic proteins such as SOD2 and GJA1 in BMSCs. In conclusion, our findings demonstrate the crucial role of PMN-EVs in promoting the osteogenic differentiation of BMSCs during bone regeneration. Furthermore, this study proposes a novel strategy for enhancing bone repair and regeneration via the integration of PMN-EVs with BMSC-based cell sheets.

Application of CRISPR/Cas12i.3 for targeted mutagenesis in broomcorn millet (Panicum miliaceum L.).

In the present study, we have successfully established a gene editing platform in broomcorn millet, one of the oldest crops originating from China, by using our CRISPR/Cas12i.3, and we also created new elite germplasm for this crop.

Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

Co-delivery of Plinabulin and Tirapazamine boosts anti-tumor efficacy by simultaneously destroying tumor blood vessels and killing tumor cells.

It is imperative to optimize chemotherapy for heightened anti-tumor therapeutic efficacy. Unrestrained tumor cell proliferation and sustained angiogenesis are pivotal for cancer progression. Plinabulin, a vascular disrupting agent, selectively destroys tumor blood vessels. Tirapazamine (TPZ), a hypoxia-activated prodrug, intensifies cytotoxicity in diminishing oxygen levels within tumor cells. Despite completing Phase III clinical trials, both agents exhibited modest treatment efficiency due to dose-limiting toxicity. In this study, we employed methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PDLLA) to co-deliver Plinabulin and TPZ to the tumor site, concurrently disrupting blood vessels and eliminating tumor cells, addressing both symptoms and the root cause of tumor progression. Plinabulin was converted into a prodrug with esterase response (PSM), and TPZ was synthesized into a hexyl chain-containing derivative (TPZHex) for effective co-delivery. PSM and TPZHex were co-encapsulated with mPEG-b-PDLLA, forming nanodrugs (PT-NPs). At the tumor site, PT-NPs responded to esterase overexpression, releasing Plinabulin, disrupting blood vessels, and causing nutritional and oxygen deficiency. TPZHex was activated in response to increased hypoxia, killing tumor cells. In treating 4T1 tumors, PT-NPs demonstrated enhanced therapeutic efficacy, achieving a 92.9 % tumor suppression rate and a 20 % cure rate. This research presented an innovative strategy to enhance synergistic efficacy and reduce toxicity in combination chemotherapy.

Co-sensitization of Copper Indium Gallium Disulfide and Indium Sulfide on Zinc Oxide Nanostructures: Effect of Morphology in Electrochemical Carbon Dioxide Reduction.

Recent advances in nanoparticle materials can facilitate the electro-reduction of carbon dioxide (CO2) to form valuable products with high selectivity. Copper (Cu)-based electrodes are promising candidates to drive efficient and selective CO2 reduction. However, the application of Cu-based chalcopyrite semiconductors in the electrocatalytic reduction of CO2 is still limited. This study demonstrated that novel zinc oxide (ZnO)/copper indium gallium sulfide (CIGS)/indium sulfide (InS) heterojunction electrodes could be used in effective CO2 reduction for formic acid production. It has been determined that Faradaic efficiencies for formic acid production using ZnO nanowire (NW) and nanoflower (NF) structures vary due to structural and morphological differences. A ZnO NW/CIGS/InS heterojunction electrode resulted in the highest efficiency of 77.2% and 0.35 mA cm-2 of current density at a -0.24 V (vs. reversible hydrogen electrode) bias potential. Adding a ZTO intermediate layer by the spray pyrolysis method decreased the yield of formic acid and increased the yield of H2. Our work offers a new heterojunction electrode for efficient formic acid production via cost-effective and scalable CO2 reduction.

Metabolic Reprogramming: A Byproduct or a Driver of Cardiomyocyte Proliferation?

Defining mechanisms of cardiomyocyte proliferation should guide the understanding of endogenous cardiac regeneration and could lead to novel treatments for diseases such as myocardial infarction. In the neonatal heart, energy metabolic reprogramming (phenotypic alteration of glucose, fatty acid, and amino acid metabolism) parallels cell cycle arrest of cardiomyocytes. The metabolic reprogramming occurring shortly after birth is associated with alterations in blood oxygen levels, metabolic substrate availability, hemodynamic stress, and hormone release. In the adult heart, myocardial infarction causes metabolic reprogramming but these changes cannot stimulate sufficient cardiomyocyte proliferation to replace those lost by the ischemic injury. Some putative pro-proliferative interventions can induce the metabolic reprogramming. Recent data show that altering the metabolic enzymes PKM2 [pyruvate kinase 2], LDHA [lactate dehydrogenase A], PDK4 [pyruvate dehydrogenase kinase 4], SDH [succinate dehydrogenase], CPT1b [carnitine palmitoyl transferase 1b], or HMGCS2 [3-hydroxy-3-methylglutaryl-CoA synthase 2] is sufficient to partially reverse metabolic reprogramming and promotes adult cardiomyocyte proliferation. How metabolic reprogramming regulates cardiomyocyte proliferation is not clearly defined. The possible mechanisms involve biosynthetic pathways from the glycolysis shunts and the epigenetic regulation induced by metabolic intermediates. Metabolic manipulation could represent a new approach to stimulate cardiac regeneration; however, the efficacy of these manipulations requires optimization, and novel molecular targets need to be defined. In this review, we summarize the features, triggers, and molecular regulatory networks responsible for metabolic reprogramming and discuss the current understanding of metabolic reprogramming as a critical determinant of cardiomyocyte proliferation.

Stereoselective and controllable C3-Amination or C1,C3-di-amination of 2-nitroglycals.

Precise and selective modification of carbohydrates is a critical strategy in producing diverse carbohydrate derivatives for exploiting their functions. We disclosed a simple, efficient, and highly regioselective and stereoselective protocol to controllable amination of 2-nitroglycals under mild conditions in 5 min. A range of 3-amino-carbohydrates including 3-arylamino-2-nitro-glycals and 1,3-di-amino-carbohydrate derivatives were obtained in good to excellent yield with excellent stereoselectivity. The produced 3-amino-2-nitro-glycals can be used as a precursor for further transformation.

Association between hypertensive disorders and Bell's palsy in pregnancy: protocol for a systematic review and meta-analysis.

BACKGROUND: Bell's palsy is an idiopathic peripheral nerve palsy involving the facial nerve. Pregnancy, diabetes mellitus and hypertension are the risk factors for Bell's palsy. However, the association between hypertensive disorders and Bell's palsy during pregnancy or the puerperium remains unclear. This systematic review will comprehensively summarise the literature and evaluate the association between Bell's palsy and hypertensive disorders during pregnancy or the puerperium. METHODS AND ANALYSIS: Systematic searches of PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be undertaken using prespecified search strategies. Observational studies (cross-sectional studies, cohort studies, case reports and series case reports) written in English that investigate the association between hypertensive disorders of late pregnancy and Bell's palsy during pregnancy or the puerperium will be included. Different authors will independently conduct the eligible study selection, perform data extraction and appraise the quality of included studies. Subgroup analysis will be carried out based on the age of pregnant women (≤35 years old, >35 years old), parity (primipara, multipara) and fetus number (singleton or multiple-gestation pregnancy). ETHICS AND DISSEMINATION: This review will be based on published literature, and thus there is no requirement for ethics approval. The results of this study will aid in the knowledge of the relationship between Bell's palsy during pregnancy or the puerperium and hypertensive disorders of late pregnancy. The results of this systematic review will be shared through publication in a peer-reviewed journal with good visibility for the field of obstetrics and presentations at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023422902.

Controllable 1,3-Bis-Functionalization of 2-Nitroglycals with High Regioselectivity and Stereoselectivity Enabled by a H-Bond Catalyst.

The selective modification of carbohydrates is significant for producing their unnatural analogues for drug discovery. C1-functionalization (glycosylation) and C1,C2-difunctionalization of carbohydrates have been well developed. In contrast, C3-functionalization or C1,C3-difunctionalization of carbohydrates remains rare. Herein, we report such processes that efficiently and stereoselectively modify carbohydrates. Specifically, we found that trifluoroethanol (TFE) could promote 1,3-bis-indolylation/pyrrolylation of 2-nitroglycals generated carbohydrate derivatives in up to 93% yield at room temperature; slightly reducing the temperature could install two different indoles at the C1- and C3-positions. Switching TFE to a bifunctional amino thiourea catalyst leads to the generation of C3 monosubstituted carbohydrates, which could also be used to construct 1,3-di-C-functionalized carbohydrates. This approach produced a range of challenging sugar derivatives (over 80 examples) with controllable and high stereoselectivity (single isomer for over 90% of the examples). The potential applications of the reaction were demonstrated by a set of transformations including the synthesis of bridged large-ring molecules and gram scale reactions. Biological activities evaluation demonstrated that three compounds exhibit a potent inhibitory effect on human cancer cells T24, HCT116, AGS, and MKN-45 with IC50 ranged from 0.695 to 3.548 µM.