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Drug-induced liver injury (DILI) is a major clinical issue associated with the majority of commercial drugs. During DILI, the peroxynitrite (ONOO–) level is upregulated in the liver. However, traditional methods are unable to timely monitor the dynamic changes of the ONOO–level during DILI in vivo. Therefore, ONOO–-activated near-infrared (NIR) fluorescent probes with high sensitivity and selectivity are key to the early diagnosis of DILI in situ. Herein, we report a novel ONOO–-responsive NIR fluorescent probe, QCy7-DP, which incorporates a donor-dual-acceptor π-electron cyanine skeleton with diphenyl phosphinate. The ONOO–-mediated highly selective hydrolytic cleavage via an addition-elimination pathway of diphenyl phosphinate produced the deprotonated form of QCy7in physiological conditions with a distinctive extended conjugated π-electron system and ∼200-fold enhancement in NIR fluorescence emission at 710 nm. Moreover, the probe QCy7-DPwas successfully used for the imaging of the endogenous and exogenous ONOO–concentration changes in living cells. Importantly, in vivofluorescence imaging tests demonstrated that the probe can effectively detect the endogenous generation of ONOO–in an acetaminophen (APAP)-induced liver injury mouse model. This study provides insight into the design of highly selective NIR fluorescent probes suitable for spatiotemporal monitoring of ONOO–under different pathological conditions.

Fluorescent silicon nanodots have shown great prospects for bioimaging and biosensing applications. Although various fluorescent silicon-containing nanodots (SiNDs) have been developed, there are few reports about renal-clearable multicolor SiNDs. Herein, renal-clearable multicolor fluorescent SiNDs are synthesized by using silane molecules and organic dyes through a facile one-step hydrothermal method. The fluorescence of the resulting SiNDs can be tuned to blue (bSiNDs), green (gSiNDs), and red (rSiNDs) by simply changing the categories of silane reagents or dye molecules. The as-prepared SiNDs exhibit strong fluorescence with a quantum yield up to 72%, excellent photostability, and good biocompatibility with 12 h renal clearance rate as high as 86% ID. These properties enabled the SiNDs for tumor fluorescence imaging and H2O2imaging in living cells and tissue through in situ reduction reaction-lighted fluorescence of the nanoprobe. Our results provide an invaluable methodology for the synthesis of renal-clearable multicolor SiNDs and their potential applications for fluorescence imaging and biomarker sensing. These SiNDs are also promising for various biological and biomedical applications.

Background: Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients. Methods: This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n= 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n= 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches. Results: Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5–86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P< 0.001) individuals with a higher burden of comorbidities. Over a median follow-up of 10.4 years, 398 (38.8%) all-cause deaths were identified. Compared with the MICCD group, the CICCD group exhibited a higher adjusted hazard ratio (HR) (95% confidential interval, CI) of 1.71 (1.32–2.39) for long-term mortality after adjusting for potential confounders. The sensitivity analysis results remained robust. After inverse probability of treatment weighting (IPTW) modeling, the CICCD group displayed an even worse mortality risk (IPTW-adjusted HR: 2.07; 95% CI 1.47–2.90). In addition, anemia (adjusted HR: 1.48; 95% CI 1.16–1.89) and malnutrition (adjusted HR: 1.43; 95% CI 1.15–1.78) are also independent risk factors for all-cause mortality among elderly and very elderly patients. Conclusions: Our results thus suggest that elderly patients with ischemic cardio-cerebrovascular disease and anemia or malnutrition may have higher mortality, which may be predicted upon admission. These findings, however, warrant further investigation. Graphical Abstract:

Ni(benzimidazole)(2-methylimidazole) with two-dimensional structure is used as a self-template to synthesize carbon-coated Ni0.85Se (Ni0.85Se@C) composites. Ni0.85Se@C composites display a thin nanosheet structure (∼20 nm) with macropores (∼200 nm), which can effectively reduce the volume change. The carbon network can improve the electrical conductivity of the electrode material. When evaluated as anode material for sodium ion batteries (SIBs), Ni0.85Se@C composites deliver an excellent reversible capacity of 405 mA h g−1at 200 mA g−1after 100 cycles and a good rate performance with a capacity of 200 mA h g−1at 3.0 A g−1.Ni(bim)(2-mim) with two-dimensional structure is used as self-template to synthesize carbon-coated Ni0.85Se composites (Ni0.85Se@C) with numerous thin (∼20 nm) nanosheets and pores (∼200 nm), which effectively reduce the huge volume change. Ni0.85Se@C nanosheets were evaluated as anode material of SIBs, which deliver an excellent electrochemical performance.

The Sichuan Basin is rich in shale oil and gas resources, with favorable geological conditions that the other shale reservoirs in China cannot match. Thus, the basin is an ideal option for fully “exploring petroleum inside source kitchen” with respect to onshore shale oil and gas in China. This paper analyzes the characteristics of shale oil and gas resources in the United States and China, and points out that maturity plays an important role in controlling shale oil and gas composition. US shale oil and gas exhibit high proportions of light hydrocarbon and wet gas, whereas Chinese marine and transitional shale gas is mainly dry gas and continental shale oil is generally heavy. A comprehensive geological study of shale oil and gas in the Sichuan Basin reveals findings with respect to the following three aspects. First, there are multiple sets of organic-rich shale reservoirs of three types in the basin, such as the Cambrian Qiongzhusi Formation and Ordovician Wufeng Formation-Silurian Longmaxi Formation marine shale, Permian Longtan Formation transitional shale, Triassic Xujiahe Formation lake-swamp shale, and Jurassic lacustrine shale. Marine shale gas enrichment is mainly controlled by four elements: Deep-water shelf facies, moderate thermal evolution, calcium-rich and silicon-rich rock association, and closed roof/floor. Second, the “sweet section” is generally characterized by high total organic carbon, high gas content, large porosity, high brittle minerals content, high formation pressure, and the presence of lamellation/bedding and natural microfractures. Moreover, the “sweet area” is generally characterized by very thick organic-rich shale, moderate thermal evolution, good preservation conditions, and shallow burial depth, which are exemplified by the shale oil and gas in the Wufeng-Longmaxi Formation, Longtan Formation, and Daanzhai Member of the Ziliujing Formation. Third, the marine, transitional, and continental shale oil and gas resources in the Sichuan Basin account for 50%, 25%, and 30% of the respective types of shale oil and gas geological resources in China, with great potential to become the cradle of the shale oil and gas industrial revolution in China. Following the “Conventional Daqing-Oil” (i.e., the Daqing oilfield in the Songliao Basin) and the “Western Daqing-Oil & Gas” (i.e., the Changqing oilfield in the Ordos Basin), the Southwest oil and gas field in the Sichuan Basin is expected to be built into a “Sichuan-Chongqing Daqing-Gas” in China.

Background:This case series report aimed to present three surgical approaches used for the treatment of cerebrospinal fluid (CSF) otorrhea, providing less invasive surgical options for managing this condition. Methods:Clinical data of 26 patients with CSF otorrhea, who underwent treatment using three surgical methods between June 2012 and June 2022, were retrospectively analyzed. The study collected information on patients’ basic demographic characteristics, chief complaints, location of the defect, results of otorrhea endoscopic examination, findings from skull base thin-slice computed tomography (CT) examination, and causes of CSF otorrhea. Postoperative outcomes of CSF otorrhea were followed up. Results:Among the 26 cases of CSF otorrhea, there were 13 (50%) males and 13 (50%) females who underwent treatment using the three surgical methods. The etiology of CSF otorrhea included 10 (38%) cases of spontaneous CSF otorrhea, including 2 (8%) cases of congenital inner ear deformity and 8 (31%) cases without obvious inducement. Additionally, there were 5 (19%) cases of trauma, 6 (23%) cases of cholesteatoma complications, 3 (12%) cases of postoperative complications of brain tumor, 1 (4%) case of radiotherapy, and 1 (4%) case of a malignant tumor. A total of 12 (46%) cases of CSF otorrhea were treated by local repair of the defect. Furthermore, 3 (12%) cases underwent local repair of the defect combined with sealing of the tympanic sinus entrance, while 11 (42%) cases underwent local repair of the defect combined with sealing of the eustachian tube and the external auditory canal. No recurrence of CSF otorrhea was observed during the 6-month to 10-year follow-up period after surgery. Conclusion:The three methods for CSF otorrhea, including local defect repair, local defect repair combined with sealing of the tympanic sinus entrance, and sealing of the eustachian tube and the external auditory canal, demonstrated successful outcomes in appropriately selected patients.

Metabolic syndrome (MS) is a combination of symptoms characterized by central obesity, hypertension, hyperglycemia, and hyperlipidemia, which together increase the risk of heart disease, stroke and diabetes. In our study, we hypothesized that an EET-agonist (AUDA) would increase expression of PGC 1α and improve mitochondrial and endothelial functions, resulting in improved heart function in a rat model of MS. To investigate this, rats were randomly divided into four groups: 1) Control; 2) MS + ABCT; 3) MS + AUDA; and 4) MS + AUDA + SnMP. MS rats were fed a high-fructose diet for 16 weeks and developed elevated inflammatory mediators, oxidative stress, and significant decreases in fractional shortening and hemodynamic parameters, indicating cardiac dysfunction. Histology revealed myocardial fibrosis and myocyte hypertrophy. AUDA improves mitochondrial function proven by increase in mt copy number and ATP production and significantly increased expression of PGC-1α and HO-1 in the rats and normalization of inflammatory cytokines, oxidative stress, and improves in cardiac function and myocardial fibrosis. These benefits were reversed by SnMP. Furthermore, AUDA increases eNOS but decreases iNOS expression which improved endothelial function. We therefore demonstrate that endogenous EET upregulation plays a novel role in protecting the heart from MS by regulating mitochondrial and endothelial function.

Deep Wufeng–Longmaxi marine shale has abundant natural gas resources, but its complex tectonic characteristics lead to strong reservoir heterogeneity, limiting large-scale shale gas development. Herein, to clarify the effects of tectonism on shale pore structure characteristics and reservoir quality in different tectonic regions, typical shale samples from high-steep anticline (HSA) and broad-gentle syncline (BGS) were collected and analyzed through field emission scanning electron microscopy (FE-SEM), gas adsorption, high-pressure mercury injection, and field gas desorption. The results show that under stable tectonic conditions, BGS-shale develops lots of organic matter (OM) pores, and mesopores provide the main pore volume, accounting for over 75%. Deformed and damaged by tectonic extrusion, the HSA-shale is mainly composed of interparticle (InterP) pores and intraparticle (IntraP) pores, with mesopores and micropores accounting for 38.97–47.69% and 37.79–51.28% of total pore volume. Benefiting from increased microfractures and dissolution pores, the macropore volume of HSA-shale is similar to that of BGS-shale. Under good preservation and high pressure coefficient, BGS-shale has a larger pore volume, pore surface area, and porosity to store abundant shale gas, which is conducive to a high shale gas yield. However, the HSA-shale has lower shale gas storage capacity and yield because its porosity, pore volume, and pore surface area are reduced with worse preservation condition. Therefore, in complex tectonic zones, the deep BGS-shale is more favorable for shale gas development than HSA-shale.

Monitoring drug release in vitroand in vivois of paramount importance to accurately locate diseased tissues, avoid inappropriate drug dosage, and improve therapeutic efficiency. In this regard, it is promising to develop strategies for real-time monitoring of drug release inside targeted cells or even in living bodies. Thus far, many multi-functional drug delivery systems constructed by a variety of building blocks, such as organic molecules, polymeric nanoparticles, micelles, and inorganic nanoparticles, have been developed for drug release monitoring. Especially, with the advancements in imaging modalities relating to nanomaterials, there has been an increasing focus on the use of non-invasive imaging techniques for monitoring drug release and drug efficacy in recent years. In this review, we introduce the application of fluorescence imaging, magnetic resonance imaging (MRI), surface-enhanced Raman scattering (SERS), and multi-mode imaging in monitoring drug release, involving a variety of nanomaterials such as organic or inorganic nanoparticles as imaging agents; their design principles are also elaborated. Among these, a special emphasis is placed on fluorescence-based drug release monitoring strategies, followed by a brief overview of MRI, SERS, and multi-mode imaging-based strategies. In the end, the challenges and prospects of drug release monitoring are also discussed.

A practical model that uses a combination of the variations in total organic carbon (TOC) content and mineralogy is developed to determine the shale facies. By using a ternary plot, four main lithofacies and 14 subfacies were identified. This method is applied to describe the shale lithofacies and to identify the favourable lithofacies in the Wufeng and Lungmachi formations based on drill cores from well WX2, NE Sichuan Basin, China. The results show five classes of lithofacies are present and the organic-rich siliceous shale at the base of the Lungmachi Formation (LMF) is the most promising lithofacies, as it has the highest in-situ gas content, abundant TOC, and a high brittleness index, which are all favourable for the generation and development of shale gas. No significant changes in lateral continuity exist in the study area. The core based model can be used to quantify shale lithofacies in other areas.

The Sichuan Basin is a major target for shale gas exploration in present China because of its rich gas stored in abundant black shales with multiple bed series. For further guidance or reference, field exploration and development practices in the shale reservoirs Upper Ordovician Wufeng–Lower Silurian Longmaxi shale reservoirs were studied in terms of development stages and progress, favorable conditions for shale gas accumulation, bottlenecking issues on theories and technologies related to shale gas development, and so on. The following findings were obtained. (1) Shale with rich organic matters originated from the deep shelf has a good quality and great thickness in the continuous beds. The relatively stable wide buffer zones in synclines (anticlines) provides favorable conditions for shale gas accumulation and preservation with well-developed micro-fractures and overpressure as necessary factors for a great potential of high shale gas productivity. (2) The bottlenecking technical issues restricting the shale gas industrial development in this study area include the following aspects: understandings of rich-organic matter shale sedimentary facies and modes, shale reservoir diagenetic process and evaluation systems, shale gas generation and accumulation mechanism, geophysical logging identification and prediction of shale gas layers, low resource utilization rate, great uncertainty of shale gas development, no technological breakthrough in the exploration of shale gas reservoirs buried deeper than 3500 m. In conclusion, this study area will be the major target for the shale gas exploration and development in China in a rather long period in the future.

ABSTRACTA practical model that uses a combination of the variations in total organic carbon (TOC) content and mineralogy is developed to determine the shale facies. By using a ternary plot, four main lithofacies and 14 subfacies were identified. This method is applied to describe the shale lithofacies and to identify the favourable lithofacies in the Wufeng and Lungmachi formations based on drill cores from well WX2, NE Sichuan Basin, China. The results show five classes of lithofacies are present and the organic-rich siliceous shale at the base of the Lungmachi Formation (LMF) is the most promising lithofacies, as it has the highest in-situ gas content, abundant TOC, and a high brittleness index, which are all favourable for the generation and development of shale gas. No significant changes in lateral continuity exist in the study area. The core based model can be used to quantify shale lithofacies in other areas.

Background:N6-methyladenosine (m6A) methylation is dynamically regulated by writers and erasers, and ultimately affects RNA splicing, translation, and stability after by recognized readers, thereby affecting disease progression. Sunitinib (SUN) is a tyrosine kinase inhibitor (TKI) widely used to treat different types of solid and hematological tumors, but its cardiotoxicity limits its clinical application. FTO is an m6A demethylase has been shown to play an important role in various heart diseases. In this study, we deciphered the methylation modification of m6A mRNA in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) post sunitinib treatment and assessed whether FTO regulated pyroptosis-related m6A methylated transcripts in SUN-treated hiPSC-CMs.Methods and Results:The global m6A RNA-methylation level was increased in SUN-treated hiPSC-CMs and was parallel with a positively correlated cellular damage level (LDH leakage). Through a genome-wide analysis of m6A mRNA methylation by MeRIP-Seq and RNA-seq, we identified a total of 2614 peaks with significant changes. qRT-PCR, immunofluorescence, and Western blot revealed that FTO was the most evidently changed m6A modifying enzymes in SUN-treated hiPSC-CMs (downregulated fold change being 0.43). Interestingly, the loss of FTO in hiPSC-CMs exposed to SUN was positively associated with cellular damage level and pyroptosis-associated NLRP3 and ASC transcripts levels. To further test if TKI-induced increase in m6A-RNA modification is mediated through FTO loss, hiPSC-CMs, overexpressed with ectopic FTO, showed significant restoration of m6A methylation level and normalization of pyroptosis-associated transcripts (NLRP3 and ASC) after exposure to SUN. To evaluate the effect of FTO on the methylation of RNA transcripts of NLRP3 and ASC, MeRIP assay demonstrated that FTO tightly controlled the methylation levels of NLRP3 and ASC transcripts, and demethylation of these transcripts by FTO accelerated their degradation rate.Conclusion:This study revealed that TKI-induced loss of FTO may mediate the decreased m6A-RNA methylation and TKI-induced cardiotoxicity pathogenesis by dysregulating the methylation and expression of pyroptotic transcripts NLRP3 and ASC.

Background:Abnormal blood pressure (BP) is one of the most common modified risk factors for the development of cognitive impairment (CI) with increasing aging population.Objective:This study aims to investigate the association between risk factors and CI in elderly patients based on artificial intelligence (AI) analysis of BP measurements and brain magnetic resonance angiography (MRA).Methods:A total of 3221 elderly individuals undergone brain MRA were recruited into the nested case-control study from 2007 to 2021. Patients were divided into two groups according to diagnosis with or without CI. Data were collected before diagnosing CI. The stenosis rate of cerebral arteries was calculated by AI analysis of brain MRA. Four machine learning modalities were applied to establish predictive models.Results:A total of 416 cases (mean age 84.47 ± 6.50 years old) with or without CI were finally recruited into the study after matching with age and gender. Mean follow-up time was 3.46 ± 3.19 years. The number of BP measurements was 56.98 ± 77.94 times. In the univariate logistic regression model, high systolic blood pressure (SBP) (OR 1.029, 95% CIs 1.010-1.049), pulse pressure (PP) (OR 1.043, 95% CIs: 1.021-1.065) and pulse pressure index (PPI) (OR 3588.920, 95% CIs: 44.392-290148.336) increased the risk of CI. Based on various mean BP parameters, the predictive ability of the support vector machine (SVM) was improved after adding cerebral arterial stenosis rate (AUC 0.781, 95% CIs 0.639~0.923).Conclusion:Abnormal SBP, PP and PPI were risk factors for CI in the elderly Chinese population. Adding the cerebral arterial stenosis rate of internal carotid artery and posterior cerebral artery the predictive ability of SVM model of various mean BP parameters for the risk of CI was improved.

In this work, we report a facile strategy to anchor CdTe nanocrystals onto synchronously synthesized polymer for the fabrication of luminescent hollow poly(3-methacryloxypropyltrimethoxysilane) (PMPTS)/CdTe composite colloids. Firstly, glutathione-coated CdTe nanocrystals with green fluorescence were synthesized in an aqueous solution. Dithiothreitol was then introduced into the solution as co-ligand and cross-linker to bridge CdTe and prospective polymer. Subsequently, MPTS monomers and light initiator in toluene solution were added into the CdTe aqueous solution under sonication to form a semi-stable emulsion. Finally, the emulsion was light irradiated to prepare PMPTS colloids and simultaneously graft CdTe nanocrystals onto these colloids through thiol-ene click chemistry. This facile route allows the polymer synthesis and its functionalization with inorganic nanoparticles in one step, potentially leading to practical applications for building diverse hybrid structures.A facile strategy has been developed to anchor CdTe nanocrystals onto synchronously synthesized polymer for fabrication of luminescent hollow poly(3-methacryloxypropyltrimethoxysilane) (PMPTS)/CdTe composite colloids, which allows both polymer synthesis and its functionalization with inorganic nanoparticles in one step, potentially leading to practical applications for building diverse hybrid structures.

Ultrasmall glutathione-coated luminescent gold nanoparticles (GS-AuNPs) are known for their high resistance to serum protein adsorption. Our studies show that these NPs can serve as surface ligands to significantly enhance the physiological stability and lower the serum protein adsorption of superparamagnetic iron oxide nanoparticles (SPIONs), in addition to rendering the NPs the luminescence property. After the incorporation of GS-AuNPs onto the surface of SPIONs to form the hybrid nanoparticles (HBNPs), these SPIONs’ protein adsorption was about 10-fold lower than those of the pure glutathione-coated SPIONs suggesting that GS-AuNPs are capable of providing a stealth effect against serum proteins.

Mixed-flow pump is one of the most widely used general machinery, it is necessary to study the efficiency of the mixed-flow pump. In this paper, we have made a test on a mixed-flow pump model. After testing we got the conclusion that the mixed flow pump efficiency analysis of experiments in 6 different blade angle of operation, through the analysis of the status, to this model the suitable angle is-4 °.

In order to solve the problems of indoor fingerprint localization algorithm based on static weight, such as low positioning accuracy and poor environmental adaptability, a variable weight indoor based on channel state information with Euclidean distance as weight reference is proposed. In the preprocessing stage, the collected CSI amplitude values are first subjected to Butterworth low-pass filtering denoising processing, and then the values of each sampling point are averaged, and the reference point location fingerprint database is established by combining the known coordinates. The weight index a is introduced in the online positioning stage, and the nearest neighbor is found by the KNN algorithm with the CSI eigenvalue reference. Then the weight index b is introduced, and the Euclidean distance is used as the weight reference, and the nearest neighbor is weighted. Get the coordinates of the target position. The experimental results show that the indoor fingerprint localization algorithm proposed by this scheme has higher positioning accuracy and less fluctuation of positioning error than the traditional KNN-based indoor fingerprint localization algorithm.