The novel BCL-2/BCL-XL inhibitor APG-1252-mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer.

HER2-positive gastric cancer has a poor prognosis, with a high incidence of drug resistance and a lack of effective treatments for drug-resistant patients. The exploration of the mechanism of resistance to HER2-targeted therapy in HER2-positive gastric cancer and the identification of effective strategies to reverse it are urgently needed. In this study, we found that HER2-targeted agents upregulated the expression of GSDME and that the overexpression of GSDME attenuated the sensitivity of HER2-targeted agents.

Fast and efficient hard X-ray projection imaging below 10 nm resolution.

High-resolution X-ray imaging of noncrystalline objects is often achieved through the approach of scanning coherent diffractive imaging known as ptychography. The imaging resolution is usually limited by the scattering properties of the sample, where weak diffraction signals at the highest scattering angles compete with parasitic scattering. Here, we demonstrate that X-ray multilayer Laue lenses with a high numerical aperture (NA) can be used to create a strong reference beam that holographically boosts weak scattering from the sample over a large range of scattering angles, enabling high-resolution imaging that is tolerant of such background.

Role of slice thickness quantification in the 3D reconstruction of FIB tomography data of nanoporous materials.

In focused ion beam (FIB) tomography, a combination of FIB with a scanning electron microscope (SEM) is used for collecting a series of planar images of the microstructure of nanoporous materials. These planar images serve as the basis for reconstructing the three-dimensional microstructure through segmentation algorithms. However, the assumption of a constant distance between consecutively imaged sections is generally invalid due to random variations in the FIB milling process.

Co-Colorectal cancer stem cells employ the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.

Colorectal cancer (CRC) ranks as China's second most common cancer and fifth top cancer death cause. The study highlights the role of Natural Killer (NK) cells in targeting cancer stem cells (CSCs) that evade immune responses in CRC. Colorectal cancer stem cells (CCSCs) were stem from HT-29 cells and co-cultured with NK cells under normoxic or hypoxic conditions.

Intravenous bolus injection of fentanyl triggers an immediate central and upper airway obstructive apnea via activating vagal sensory afferents.

Intravenous bolus (IVb) injection of fentanyl induces an immediate apnea, but the characteristics of the apnea and relevant mechanism remain unclear. Here, we tested whether IVb injection of fentanyl induced an immediate central and upper airway obstructive apnea associated with chest wall rigidity via activating vagal C-fibers (VCFs) and vagal afferent opioid receptors (ORs). Cardiorespiratory and electromyography of external and internal intercostal, thyroarytenoid, and superior pharyngeal constrictor muscles (EMG, EMG, EMG and EMG) responses to IVb injection of fentanyl were recorded in anesthetized and spontaneously breathing rats with or without bilateral perivagal capsaicin treatment or intravagal microinjection of naloxone.

A miR-383-5p Signaling Hub Coordinates the Axon Regeneration Response to Inflammation.

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular inflammation to identify their potential role in axon regeneration.

Cardiorespiratory failure induced by inhalation of aerosolized fentanyl in anesthetized rats.

Intravenous rapid injection of fentanyl causes respiratory depression (severe apneas), leading to sudden death, which constitutes the deadliest drug reaction among overdoses of synthetic opioids. Here we asked whether acute inhalation of overdose fentanyl would also result in similar respiratory failure and death. The anesthetized and spontaneously breathing rats with tracheal cannulation were exposed to aerosolized fentanyl at 100 mg/m (FNT) or 30 mg/m (FNT) for 10 min.

Blood Coagulation-Inspired Fibrin Hydrogel for Portable Detection of Thrombin Based on Personal Glucometer.

As one of the biomarkers of coagulation system-related diseases, the detection of thrombin is of practical importance. Thus, this study developed a portable biosensor based on a personal glucometer for rapid detection of thrombin activity. Fibrinogen was used for the detection of thrombin, and the assay principle was inspired by the blood coagulation process, where thrombin hydrolyzes fibrinogen to produce a fibrin hydrogel, and the amount of invertase encapsulated in the fibrin hydrogel fluctuates in accordance with the activity of thrombin in the sample solution.

hP-MSCs attenuate severe acute pancreatitis in mice via inhibiting NLRP3 inflammasome-mediated acinar cell pyroptosis.

Background: Severe acute pancreatitis (SAP) is a serious gastrointestinal disease that is facilitated by pancreatic acinar cell death. The protective role of human placental mesenchymal stem cells (hP-MSCs) in SAP has been demonstrated in our previous studies. However, the underlying mechanisms of this therapy remain unclear.

Apneic response to fentanyl in adult rats: Role of laryngeal afferents.

Intravenous (systemic) bolus injection of fentanyl (FNT) reportedly induces an immediate vagal-mediated apnea; however, the precise origin of vagal afferents responsible for this apnea remains unknown. We tested whether intralaryngeal (local) application of FNT would also trigger an apnea and whether the apneic response to both local and systemic administration of FNT was laryngeal afferent-mediated. Cardiorespiratory responses to FNT were recorded in anesthetized male adult rats with and without bilateral sectioning of the superior laryngeal nerve (SLNx) or peri-SLN capsaicin treatment (SLNcap) to block local C-fiber signal conduction.

[Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis].

Objective: To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH).

Methods: Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.

Sequential targeting dual-responsive magnetic nanoparticle for improved therapy of lung metastatic breast cancer.

Lung metastatic breast cancer is a leading cause of cancer-related death in women and difficult to treat due to non-specific drug delivery. Herein a sequential targeting dual-responsive magnetic nanoparticle was fabricated, where FeO nanoparticle was used as magnetic core, then sequentially coated with tetraethyl orthosilicate, bis[3-(triethoxy-silyl)propyl] tetrasulfide, and 3-(trimethoxysilyl) propylmethacrylate to afford -C = C- on the surface for further polymerisation with acrylic acid, acryloyl-6-ethylenediamine-6-deoxy-β-cyclodextrin using N, N-bisacryloylcy- stamine as cross-linker, obtaining pH/redox dual-responsive magnetic nanoparticle (MNPs-CD) to delivery doxorubicin (DOX) for suppressing lung metastatic breast cancer. Our results suggested DOX-loaded nanoparticle could target the lung metastases site by sequential targeting, in which they first be delivered to the lung and even the metastatic nodules through size-driven, electrical interaction, and magnetic field-guided mechanisms, then be effectively internalised into the cancer cells followed by intelligently triggering DOX release.

AURKA Identified as Potential Lung Cancer Marker through Comprehensive Bioinformatic Analysis and Experimental Verification.

Non-small-cell lung cancer (NSCLC) is a malignancy with high overall morbidity and mortality due to a lack of reliable methods for early diagnosis and successful treatment of the condition. We identified genes that would be valuable for the diagnosis and prognosis of lung cancer. Common DEGs (DEGs) in three GEO datasets were selected for KEGG and GO enrichment analysis.

Integrative bioinformatics approaches to establish potential prognostic immune-related genes signature and drugs in the non-small cell lung cancer microenvironment.

Research has revealed that the tumor microenvironment (TME) is associated with the progression of malignancy. The combination of meaningful prognostic biomarkers related to the TME is expected to be a reliable direction for improving the diagnosis and treatment of non-small cell lung cancer (NSCLC). Therefore, to better understand the connection between the TME and survival outcomes of NSCLC, we used the "DESeq2" R package to mine the differentially expressed genes (DEGs) of two groups of NSCLC samples according to the optimal cutoff value of the immune score through the ESTIMATE algorithm.

The Roles of Exosomes in the Diagnose, Development and Therapeutic Resistance of Oral Squamous Cell Carcinoma.

Oral cancer is one of the most common cancers worldwide, of which more than half of patients are diagnosed at a locally advanced stage with poor prognosis due to recurrence, metastasis and resistant to treatment. Thus, it is imperative to further explore the potential mechanism of development and drug resistance of oral cancer. Exosomes are small endosome-derived lipid nanoparticles that are released by cells.

3-Dimensional Immunostaining and Automated Deep-Learning Based Analysis of Nerve Degeneration.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease driven by inflammation and demyelination in the brain, spinal cord, and optic nerve. Optic neuritis, characterized by inflammation and demyelination of the optic nerve, is a symptom in many patients with MS. The optic nerve is the highway for visual information transmitted from the retina to the brain.

Lasso-Logistic regression model for the identification of serum biomarkers of neurotoxicity induced by strychnos alkaloids.

As a traditional Chinese medicine, strychnos alkaloids have wide effects including antitumor, analgesic, and anti-inflammatory. However, the therapeutic window of strychnos alkaloids is quite narrow due to potential neurotoxicity. Therefore, it is necessary to explore some efficient biomarkers to identify and predict the neurotoxicity induced by strychnos alkaloids and find a therapy to prevent the neurotoxicity of strychnos alkaloids.

Untouched isolation enables targeted functional analysis of tumour-cell-derived extracellular vesicles from tumour tissues.

To accurately identify the functions of tumour-cell-derived extracellular vesicles (T-EVs), EVs directly isolated from tumour tissues are much preferred over those derived from in vitro cultured tumour cell lines. However, the functional analysis of T-EVs has still been severely limited by the difficulty in selective isolation of T-EVs from tissue-derived heterogeneous EVs, which also contain non-tumour cell-derived EVs. We here establish an untouched isolation strategy that specifically collects natural T-EVs from tumour tissues by removing non-tumour-cell-derived EVs.

Analysis of serum hepatitis B virus RNA levels among HBsAg and HBsAb copositive patients and its correlation with HBV DNA.

There are approximately 2 billion HBV-infected individuals worldwide, and approximately 1.87% to 7% of these individuals are copositive for HBsAg and HBsAb.Our study detected hepatitis B virus pgRNA (HBV RNA) levels in HBsAg and HBsAb copositive patients and then analyzed the correlation with HBV DNA, HBsAg, ALT, and AST levels.

[Retracted] Downregulation of caspase‑3 alleviates ‑induced apoptosis in alveolar epithelial cells.

Following the publication of the above paper, the authors contacted the Editorial Office to request that the article be retracted on account of the presented results being unreliable; essentially, the authors did not repeat their experiments the requisite number of times, and they were unable to identify in subsequent experiments any increase in the apoptotic rate of the alveolar epithelial cells as had been reported. The Editor of has agreed that this paper should be retracted from the Journal. The Editor and the authors apologize to the readership for any inconvenience caused.

Identification of components of Caoguo using accelerated solvent extraction combined with gas chromatography-mass spectrometry integrated with network pharmacology on indigestion.

Background: Caoguo (), a traditional Chinese medicine, is widely used as medicine and dietary spices. Volatile components are among its important bioactive constituents used to treatment of abdominal distension and pain, but the mechanism is not clear up to now. The purpose of this study was to develop a simple, sensitive, and accurate method to analyze and identify components of Caoguo and , and further investigate the therapeutic mechanism of Caoguo on indigestion using network pharmacology.

ctc-[Pt(NH)(cinnamate)(valproate)Cl] is a highly potent and low-toxic triple action anticancer prodrug.

Pt(iv) prodrugs have gained tremendous attention due to their indisputable advantages compared to cisplatin. Herein, new Pt(iv) derivatives with cinnamic acid at the first axial position, and inhibitor of matrix metalloproteinases-2 and -9, histone deacetylase, cyclooxygenase or pyruvate dehydrogenase at the second axial position are constructed to develop multi-action prodrugs. We demonstrate that Pt(iv) prodrugs are reducible and have superior antiproliferative activity with IC values at submicromolar concentrations.

The need for race-specific reference equations for pulmonary diffusing capacity for nitric oxide.

Background: Few reference equations exist for healthy adults of various races for pulmonary diffusing capacity for nitric oxide (DLNO). The purpose of this study was to collect pilot data to demonstrate that race-specific reference equations are needed for DLNO.

Methods: African Americans (blacks) were chosen as the comparative racial group.