[Spatial and Temporal Characteristics and Controlling Factors of Water Quality of the Dahei River in the Yellow River Basin].

As an important ecological security barrier and an economic core belt for population activities, the Yellow River Basin plays an important role in China's social development and ecological security. To investigate the spatial and temporal changes in the water environmental quality of typical tributaries in the basin and the factors affecting them, this study was based on 12 aspects of water environmental data and month-by-month rainfall and runoff data from 21 monitoring stations in the Dahei River Basin from 2013 to 2022. The entropy-weighted water quality index （EWQI）, stepwise multiple linear regression, hierarchical cluster analysis, and Pearson correlation analysis were used to comprehensively assess the changes in the water quality of the basin and to investigate the factors controlling the water quality.

Chemically engineered antibodies for autophagy-based receptor degradation.

Cell surface receptor-targeted protein degraders hold promise for drug discovery. However, their application is restricted because of the complexity of creating bifunctional degraders and the reliance on specific lysosome-shuttling receptors or E3 ubiquitin ligases. To address these limitations, we developed an autophagy-based plasma membrane protein degradation platform, which we term AUTABs (autophagy-inducing antibodies).

Distinct Amino Acid-Based PROTACs Target Oncogenic Kinases for Degradation in Non-Small Cell Lung Cancer (NSCLC).

Proteolysis-targeting chimeras (PROTACs) selectively eliminate detrimental proteins by exploiting the ubiquitin-proteasome system (UPS), representing a promising therapeutic strategy against various diseases. Effective adaptations of degradation signal sequences and E3 ligases for PROTACs remain limited. Here, we employed three amino acids─Gly, Pro, and Lys─as the ligand to recruit the corresponding E3 ligases: CRL2, GID4, and UBRs, to degrade EML4-ALK and mutant EGFR, two oncogenic drivers in NSCLC.

Polyethylenimine Triggers Dll4 Degradation to Regulate Angiogenesis In Vitro.

The Dll4-Notch signaling pathway plays a crucial role in the regulation of angiogenesis and is a promising therapeutic target for diseases associated with abnormal angiogenesis, such as cancer and ophthalmic diseases. Here, we find that polyethylenimine (PEI), a cationic polymer widely used as nucleic acid transfection reagents, can target the Notch ligand Dll4. By immunostaining and immunoblotting, we demonstrate that PEI significantly induces the clearance of cell-surface Dll4 and facilitates its degradation through the lysosomal pathway.

Effects of coal mining and climate-environment factors on the evolution of a typical Eurasian grassland.

Coal mining can significantly impact vegetation evolution, yet the limited information on its patterns and driving factors hampers efforts to mitigate these effects and reclaim abandoned mines. This study aimed to 1) examine vegetation evolution in a semiarid steppe watershed in northeast China; and 2) characterize the driving factors behind this evolution. We analyzed the impact of twelve selected driving factors on fractional vegetation coverage (FVC) from 2000 to 2021 using a dimidiate pixel model, Sen's slope analysis, Mann-Kendall trend test, coefficient of variation analysis, and Geodetector model.

[Hydrochemical Characteristics and Control Factors of Groundwater in the Northwest Salt Lake Basin].

Taking the Tugeligaole sub-basin of the Jilantai Salt Lake Basin in Inner Mongolia as the typical study area, the groundwater samples of 22 points were collected, and their main characteristic indexes were tested during the wet season and the dry season separately in 2021. Mathematical statistics, Piper triangular diagrams, a Gibbs plot, ionic relations, and factor analysis were used to analyze and discuss the hydrochemical characteristics and formation mechanism of groundwater in different periods. Based on the evaluation of the groundwater quality using the water quality index(WQI) method, the potential risks of groundwater Cr and F were evaluated using the health risk evaluation model.

Single amino acid-based PROTACs trigger degradation of the oncogenic kinase BCR-ABL in chronic myeloid leukemia (CML).

Proteolysis-targeting chimera (PROTAC) that specifically targets harmful proteins for destruction by hijacking the ubiquitin-proteasome system is emerging as a potent anticancer strategy. How to efficiently modulate the target degradation remains a challenging issue. In this study, we employ a single amino acid-based PROTAC, which uses the shortest degradation signal sequence as the ligand of the N-end rule E3 ubiquitin ligases to degrade the fusion protein BCR (breakpoint cluster region)-ABL (Abelson proto-oncogene), an oncogenic kinase that drives the progression of chronic myeloid leukemia.

Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation.

As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin- and lysosome-dependent manner.

SGLT2 inhibitors improve kidney function and morphology by regulating renal metabolic reprogramming in mice with diabetic kidney disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. SGLT2 inhibitors are clinically effective in halting DKD progression. However, the underlying mechanisms remain unclear.

A nanomaterial targeting the spike protein captures SARS-CoV-2 variants and promotes viral elimination.

The global emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can only be solved with effective and widespread preventive and therapeutic strategies, and both are still insufficient. Here, we describe an ultrathin two-dimensional CuInPS (CIPS) nanosheet as a new agent against SARS-CoV-2 infection. CIPS exhibits an extremely high and selective binding capacity (dissociation constant (K) < 1 pM) for the receptor binding domain of the spike protein of wild-type SARS-CoV-2 and its variants of concern, including Delta and Omicron, inhibiting virus entry and infection in angiotensin converting enzyme 2 (ACE2)-bearing cells, human airway epithelial organoids and human ACE2-transgenic mice.

Synthesis of 5-Chromeno[2,3-]pyrimidin-5-one Derivatives via Microwave-Promoted Multicomponent Reaction.

A microwave-promoted multicomponent reaction of 3-formylchromones, amines, and paraformaldehyde was achieved under catalyst-free and solvent-free conditions, delivering 5-chromeno[2,3-]pyrimidin-5-one derivatives in good to excellent yields via an unexpected annulation pathway, which further expanded the synthetic application of paraformaldehyde as a C1 building block.

Dearomatization-rearomatization strategy of tyrosine for peptide/protein modification through thiol-addition reactions.

We have developed a dearomatization-rearomatization strategy for the modification of peptides/proteins through a thiol-Michael addition to the electrophilic cyclohexadienone intermediate that is generated the oxidation of tyrosine. This strategy enriches the conjugation toolbox and has great potential for applications in medicinal chemistry and chemical biology.

Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase.

Although nanomaterials have shown promising biomedical application potential, incomplete understanding of their molecular interactions with biological systems prevents their inclusion into mainstream clinical applications. Here we show that black phosphorus (BP) nanomaterials directly affect the cell cycle's centrosome machinery. BP destabilizes mitotic centrosomes by attenuating the cohesion of pericentriolar material and consequently leads to centrosome fragmentation within mitosis.

A novel pyrrole-imidazole polyamide targets Aurora kinase A and suppresses tumor growth in vivo.

Aurora kinase A (Aurora A) plays a critical role in regulating cell mitotic progression and has been considered as a promising drug target for cancer therapy. To develop a novel molecule targeting Aurora A with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide (PIP) Hoechst conjugate, PIP-Ht, targeting to a cell-cycle regulated DNA sequence locating at the promoter of human Aurora A gene (AURKA). PIP-Ht potently suppressed AURKA promoter activities, mRNA expression and protein level, induced tumor cell cycle delay and inhibited tumor cell proliferation in vitro.

Tyrosine-Specific Modification via a Dearomatization-Rearomatization Strategy: Access to Azobenzene Functionalized Peptides.

Azobenzene functionalized peptides are of great importance in photoresponsive biosystems and photopharmacology. Herein, we report an efficient approach to prepare azobenzene functionalized peptides through late-stage modification of tyrosine-containing peptides using a dearomatization-rearomatization strategy. This approach shows good chemoselectivity and site selectivity as well as sensitive group tolerance to various peptides.

Characteristics and environmental driving factors of water transformation in the Balaguer River watershed of Inner Mongolia steppe.

Inner Mongolian steppe is one of the ecological barriers in China. The variation of water resources is very important for the development of social-economy and the protection of eco-environment. We collected 254 water samples of precipitation, river, and shadow groundwater during wet-season and dry-season of 2018-2019 from Balaguer River watershed and meansured the physical-chemical indicators, δD and δO of water samples.

Coibamide A kills cancer cells through inhibiting autophagy.

Natural products are useful tools for biological mechanism research and drug discovery. Due to the excellent tumor cell growth inhibitory profile and sub-nanomolar potency, Coibamide A (CA), an N-methyl-stabilized depsipeptide isolated from marine cyanobacterium, has been considered as a promising lead compound for cancer treatment. However, the molecular anti-cancer mechanism of the action of CA remains unclear.

Novel -Methylated Cyclodepsipeptide Prodrugs for Targeted Cancer Therapy.

Coibamide A () is a highly -methylated cyclodepsipeptide with low nanomolar antiproliferative activities against various cancer cell lines. In previous work, we discovered a simplified analogue, [MeAla3-MeAla6]-coibamide (), which exhibited the same inhibitory abilities as coibamide A. Herein, to reduce the whole-body toxicity and improve the solubility of , two novel peptide-drug conjugates RGD-SS-CA () and RGD-VC-CA () were designed, synthesized, and evaluated.

A systematic review and meta-analysis of combined carotid endarterectomy with ipsilateral proximal intervention (hybrid approach) for tandem carotid artery lesions.

Objective: The safety and effectiveness of using the hybrid approach to treat tandem carotid lesions is controversial, and the clinical significance of the technical variants on the perioperative outcomes has not been evaluated. The present meta-analysis was performed to evaluate the technique, safety, effectiveness, and long-term outcomes of the hybrid approach.

Methods: The PubMed, Embase, and Cochrane Library databases were searched to identify studies from January 1, 1996 to January 11, 2020.

Infrapopliteal endovascular intervention and the angiosome concept: intraoperative real-time assessment of foot regions' blood volume guides and improves direct revascularization.

Objective: There is no consensus for determining which vessel should be revascularized in patients with multiple diseased infrapopliteal arteries. The angiosome concept may guide a more efficient targeted direct revascularization. Therefore, we conducted a study to assess whether the regional evaluation of foot blood volume may guide direct revascularization (DR) and if it will lead to better perfusion improvement than indirect revascularization (IR).

Chlorotoxin-derived bicyclic peptides for targeted imaging of glioblastomas.

A convenient and efficient strategy was developed for accessing chlorotoxin-derived bicyclic peptide-biomolecule conjugates by cyclizing fully-unprotected linear peptides with a designed tetrafunctional chemical linker. Among these peptides, bicycle-P3 bearing the N-terminal sequence of chlorotoxin shows high tumor selectivity and penetration ability, which is promising for treatment of gliomas.

Long-term outcomes of conservative treatment and endovascular treatment in patients with symptomatic spontaneous isolated superior mesenteric artery dissection: a single-center experience.

Background: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disorder, and the treatment strategies remain controversial. This study aimed to compare outcomes of conservative and endovascular treatments in symptomatic patients with SISMAD.

Methods: Forty-two consecutive SISMAD patients who were admitted to a single center between October 2009 and May 2018 were enrolled in this study.

One-year results of drug-coated balloons for long and occlusive Femoropopliteal artery disease: a single-arm trial.

Background: The performance of drug-coated balloons (DCBs) in femoropopliteal interventions has been proven through randomized trials in short lesions and lesions with relatively low proportion of occlusions. There is limited evidence of DCBs in long or occlusive lesions. This study is to investigate the efficacy of the paclitaxel-coated balloon for treatment of long and occlusive femoropopliteal arterial lesions.

Endovascular Treatment for Infrarenal Aortic Occlusion: A Systematic Review and Meta-Analysis.

Background: This study aimed to synthesize data from recently published literature to evaluate the safety and efficacy of endovascular treatment (EVT) for infrarenal aortic occlusion (IAO).

Methods: The PubMed and Embase were searched to identify all studies reporting EVT for IAO from January 1st, 2000 to December 31st, 2017. Information about patients' characteristics, comorbidities, technical success, mortality, complications, and patency was collected and analyzed.