A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants.

PJA1-mediated suppression of pyroptosis as a driver of docetaxel resistance in nasopharyngeal carcinoma.

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells.

Use of 3D Echocardiography Facilitates Analysis of Thrombolytic Efficacy in Patients With Persistent Atrial Fibrillation.

This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation. During follow-up after 9-24 weeks of rivaroxaban treatment, patients were divided into "effective group" (n = 143) and "ineffective group" (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAAD mean ), angle between left atrial appendage and left atrium (LAA-A), velocity of blood flow in left atrial appendage (LAA-v), and thrombus size were compared before and after drug administration.

Association Between Intraoperative Noradrenaline Infusion and Outcomes in Older Adult Patients Undergoing Major Non-Cardiac Surgeries: A Retrospective Propensity Score-Matched Cohort Study.

Background: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes.

A randomized controlled trial to compare the live birth rate of the first frozen embryo transfer following the progestin-primed ovarian stimulation protocol vs. the antagonist protocol in women with an anticipated high ovarian response.

Objective: To compare the live birth rate of the first frozen embryo transfer (FET) after ovarian stimulation by the progestin-primed ovarian stimulation (PPOS) protocol vs. the antagonist protocol in women with an anticipated high ovarian response who were undergoing in vitro fertilization.

Design: Randomized controlled trial.

[Characteristics of Light Absorption, Sources, and Seasonal Variation of Atmospheric Brown Carbon in Northern Nanjing].

Brown carbon (BrC) refers to a group of organic compounds in fine atmospheric particles (PM) that are able to absorb light in the ultraviolet and visible range. They have a significant impact on the visibility of air and on the earth's climate. In this study, we used a black carbon analyzer (Model AE33) to conduct field measurements in northern suburban Nanjing from March 2021 to February 2022.

Persulfate promoted carbamoylation of -arylacrylamides and -arylcinnamamides with 4-carbamoyl-Hantzsch esters.

Carbamoyl-Hantzsch esters were used as carbamoyl radical precursors for oxidative carbamoylation of -arylacrylamides and -arylcinnamamides in the presence of inexpensive persulfates. This protocol can be applied to a broad range of substrates with various functional groups, providing a variety of 3,3-disubstituted oxindoles and 3,4-disubstituted dihydroquinolin-2(1)-ones in moderate to good yields an intermolecular addition/cyclization process.

The safety of perioperative dexamethasone with antiemetic dosage in surgical patients with diabetes mellitus: a systematic review and meta-analysis.

Background: Dexamethasone is commonly used for antiemesis in surgical patients. It has been confirmed that long-term steroid use increases blood glucose level in both diabetic and non-diabetic patients, it is unclear how a single dose of intravenous dexamethasone used pre/intraoperatively for postoperative nausea and vomiting (PONV) prophylaxis would influence the blood glucose and wound healing in diabetic patients.

Methods: The Pubmed, Cochrane Library, Embase, Web of Science databases, CNKI and Google Scholar were searched.

Development and Validation of a Nomogram for Predicting Postoperative Pulmonary Infection in Patients Undergoing Lung Surgery.

Objectives: To develop and validate a nomogram for predicting postoperative pulmonary infection (PPI) in patients undergoing lung surgery.

Design: Single-center retrospective cohort analysis.

Setting: A university-affiliated cancer hospital PARTICIPANTS: A total of 1,501 adult patients who underwent lung surgery from January 2018 to December 2020.

Cross-dehydrogenative Coupling of N-Aryl Tetrahydroisoquinolines Catalyzed by an Anthraquinone-containing Polymeric Photosensitizer.

This work reports the photocatalytic application of an anthraquinone-containing polymeric photosensitizer (AQ-PHEMA) in the visible light-induced cross-dehydrogenative-coupling of N-aryl tetrahydroisoquinolines with several nucleophiles, including nitromethane, 1-methyl-2-alkyl ketone and dialkyl (aryl) phosphine oxide. The results revealed that the reaction could be catalyzed by AQ-PHEMA efficiently to afford a series of 1-substituted-2-aryl-1,2,3,4-tetrahydroisoquinolines in good to excellent yields with nice substrate tolerance under aerobic conditions at room temperature. The practical application potential was also showcased by a gram-scale synthesis.

Photoredox Generation of N-Centered Hydrazonyl Radicals Enables the Construction of Dihydropyrazole-Fused -Difluoroalkenes.

An efficient visible-light-promoted N-radical-mediated tandem radical cyclization/defluorinated alkylation of β,γ-unsaturated hydrazones, and α-trifluoromethyl alkenes is described. This protocol provides a general and effective route to synthesize various dihydropyrazole-fused -difluoroalkenes at moderate to excellent yields under redox-neutral, metal-free, and mild conditions.

Development of a Comorbidity-Based Nomogram to Predict Survival After Salvage Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era.

Purpose: To assess the impact of comorbidity on treatment outcomes in patients with locally recurrent nasopharyngeal carcinoma (lrNPC) using intensity-modulated radiotherapy (IMRT) and to develop a nomogram that combines prognostic factors to predict clinical outcome and guide individual treatment.

Methods: This was a retrospective analysis of patients with lrNPC who were reirradiated with IMRT between 2003 and 2014. Comorbidity was evaluated by Adult Comorbidity Evaluation-27 grading (ACE-27).

Synthesis of Monofluoroalkenes through Visible-Light-Promoted Defluorinative Alkylation of -Difluoroalkenes with 4-Alkyl-1,4-dihydropyridines.

In this study, a facile and efficient method to synthesize monofluoroalkenes by photoredox catalytic defluorinative alkylation of -difluoroalkenes with 4-alkyl-1,4-dihydropyridines under mild conditions (room temperature) is described. This novel strategy is applicable for a broad range of -difluoroalkene substrates with good functional group tolerance and a variety of 4-alkyl-1,4-dihydropyridines (including primary, secondary, and even tertiary alkyl radicals). Moreover, it also allows the challenging radical coupling with glycosyl-based 4-alkyl-1,4-dihydropyridines (DHPs) to synthesize monofluoroalkenylated saccharides.

Polypyrrole/polylactic acid nanofibrous scaffold cotransplanted with bone marrow stromal cells promotes the functional recovery of spinal cord injury in rats.

Aims: The objective of this study was to analyze the efficacy of polypyrrole/polylactic acid (PPy/PLA) nanofibrous scaffold cotransplanted with bone marrow stromal cells (BMSCs) in promoting the functional recovery in a rat spinal cord injury (SCI).

Methods: Female Sprague-Dawley rats were randomly divided into three groups (n = 18/group): control group, PPy/PLA group, and PPy/PLA/BMSCs group. The SCI was induced in all rats.

Rhodium(III)-Catalyzed Meta-Selective C-H Alkenylation of Phenol Derivatives.

Rhodium(III)-catalyzed remote meta-selective-C-H alkenylation of phenol derivatives has been developed using a traceless organosilicon template as the directing group. This transformation proceeds smoothly with good yields and high meta-selectivities toward a series of phenol and alkene substrates. In addition, this protocol provides an effective strategy for late-stage transformations of various meta-alkenylated aromatic compounds.

Femto/nano-second switchable passively mode-locked fiber laser with analytic modeling by the cubic-quintic Ginzburg-Landau equation.

We report a passively mode-locked erbium-doped fiber laser with pulse widths switchable from 473 fs to 76.8 ns, where the fundamental mode-locking, noise-like pulse, nanosecond mode-locking, and dual-width mode-locking (DML) are obtained by adjusting a polarization controller. Co-existence of femto- and nano-second pulses in DML is attributed to the gain balancing.

Efficacy of intermittent pneumatic compression for venous thromboembolism prophylaxis in patients undergoing gynecologic surgery: A systematic review and meta-analysis.

We sought to comprehensively assess the efficacy of Intermittent Pneumatic Compression (IPC) in patients undergoing gynecologic surgery. A computerized literature search was conducted in Pubmed, Embase and Cochrane Library databases. Seven randomized controlled trials involving 1001 participants were included.

Progressive compensatory symbiosis: spouse caregiver experiences of caring for persons with dementia in Taiwan.

Objectives: Spouse caregivers have been the predominant family members who care for persons with dementia in Taiwan. Although studies in western countries have described the caregiving experiences and changes in the marital relationship for these spouse caregivers, this information is lacking in Taiwan. This study explored the experiences of spouse caregivers caring for persons with dementia in Taiwan.

Stable passive optical clock generation in SOA-based fiber lasers.

Stable optical pulse trains are obtained from 1.3-μm and 1.5-μm semiconductor optical amplifier (SOA)-based fiber lasers using passive optical technology.

[Composition analysis of volatile oil of Asarum heterotropoides var. mandshuricum extracted by three different methods].

Objective: To study the differences of the constituents of the volatile oil from Asarum heterotropoides var. mandshuricum with three different extracted methods.

Methods: Volatile oil from Asarum heterotropoides var.

A TrkB-STAT3-miR-204-5p regulatory circuitry controls proliferation and invasion of endometrial carcinoma cells.

Background: We previously identified TrkB as an oncogene involved in promoting metastasis in endometrial carcinoma (EC). Here, we sought to delineate the effect of changes in TrkB expression on the global profile of microRNAs (miRNAs) in EC cells and further investigated the correlation between the expression of certain miRNA and TrkB in the clinicopathologic characteristics of EC patients.

Methods And Results: Using quantitative reverse transcription-PCR (qRT-PCR), we found that expression of TrkB mRNA has no significant difference in transcript levels between normal endometrium and EC cells captured by laser capture microdissection, while immunohistochemistry results demonstrated a markedly higher expression of TrkB protein in EC tissues.

Rhodamine-based 'turn-on' fluorescent probe for Cu(II) and its fluorescence imaging in living cells.

A novel rhodamine spirolactam derivative 3',6'-Bis(diethylamino)-2-(2-hydroxyethylamino) spiro[isoindoline-1,9'-xanthen]-3-one (RO1) was synthesized, and characterized by high-resolution mass spectrometry (HRMS), X-ray crystallography, Infrared spectroscopy (IR), and (1)H NMR and (13)C NMR spectroscopy. RO1 exhibited highly sensitive and exclusively selective fluorescence response toward Cu(2+) over other metal ions with a detection limit of 0.56ppb in mixed aqueous solution.

[A three-dimensional finite element study of the temporomandibular joint with different curve of Spee].

Objective: To analyze the stress distribution in temporomandibular joint (TMJ) with different depth of curve of Spee (CS) by three-dimensional finite element model (3D-FEM).

Methods: FEM with different depth of CS were established. The depth was 2.