An mRNA Display Approach for Covalent Targeting of a Virulence Factor.

() is an opportunistic human pathogen that causes over one million deaths around the world each year. We recently identified a family of serine hydrolases termed fluorophosphonate binding hydrolases (Fphs) that play important roles in lipid metabolism and colonization of a host. Because many of these enzymes are only expressed in bacteria, they are valuable targets for diagnostics and therapeutics.

A novel ypN-TRG staging system for gastric cancer patients after neoadjuvant therapy based on the metro-ticket paradigm: a multicenter and large sample retrospective analysis.

Background: Conventional ypT category evaluates the depth of invasion after neoadjuvant therapy (NAT) for gastric cancer (GC) and has limited prognostic value. Tumor regression grade (TRG) measures the extent of tumor response to treatment, and when combined with the ypN category, it may enhance the prediction of patient outcomes. This study aims to develop a new staging system by integrating TRG and ypN category to better evaluate the prognosis of GC patients receiving NAT.

Inflammatory burden index as a prognostic marker in patients with advanced gastric cancer treated with neoadjuvant chemotherapy and immunotherapy.

Background: Blood inflammation index has been shown to correlate with the prognosis of patients with gastric cancer. However, few studies have compared the efficacy of existing blood inflammatory markers in predicting the prognosis of patients with locally advanced gastric cancer in combination with neoadjuvant chemotherapy and immunotherapy.

Objective: The objective of this study was to compare the prognostic value of existing commonly used blood inflammatory index in patients with advanced gastric cancer treated with neoadjuvant chemotherapy combined with immunotherapy.

Dual Inhibitors of SARS-CoV-2 3CL Protease and Human Cathepsin L Containing Glutamine Isosteres Are Anti-CoV-2 Agents.

SARS-CoV-2 3CL protease (Main protease) and human cathepsin L are proteases that play unique roles in the infection of human cells by SARS-CoV-2, the causative agent of COVID-19. Both proteases recognize leucine and other hydrophobic amino acids at the P position of a peptidomimetic inhibitor. At the P position, cathepsin L accepts many amino acid side chains, with a partial preference for phenylalanine, while 3CL-PR protease has a stringent specificity for glutamine or glutamine analogues.

An mRNA Display Approach for Covalent Targeting of a Virulence Factor.

Staphylococcus aureus () is an opportunistic human pathogen that causes over one million deaths around the world each year. We recently identified a family of serine hydrolases termed fluorophosphonate binding hydrolases (Fphs) that play important roles in lipid metabolism and colonization of a host. Because many of these enzymes are only expressed in bacteria, they are valuable targets for diagnostics and therapeutics.

SERRATE drives phase separation behaviours to regulate m6A modification and miRNA biogenesis.

The methyltransferase complex (MTC) deposits N6-adenosine (mA) onto RNA, whereas the microprocessor produces microRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B tends to form insoluble condensates with poor activity, with its level monitored by the 20S proteasome.

Reciprocal regulation of m A modification and miRNA production machineries via phase separation-dependent and -independent mechanisms.

Methyltransferase complex (MTC) deposits 6-adenosine (m A) onto RNA, whereas microprocessor produces miRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B (MTB) tends to form insoluble condensates with poor activity, with its level monitored by 20S proteasome.

The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicentre real-world clinical study.

Background: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial.

Methods: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analyzed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups.

LncRNA MACC1-AS1 induces gemcitabine resistance in pancreatic cancer cells through suppressing ferroptosis.

Pancreatic ductal adenocarcinoma (PDA) mortality is primarily attributed to metastasis and chemotherapy resistance. In this research, the long non-coding RNA MACC1-AS1 was studied, playing a significant role in regulating lipid oxidation processes. This regulation could further lead to the inhibition of ferroptosis induced by chemotherapeutic drugs, making it a contributing factor to gemcitabine resistance in PDA.

Molecular Simulation of Surfactant Displacement of Residual Oil in Nanopores: Formation of Water Channels and Electrostatic Interaction.

The water-oil-rock system's surfactant and electrostatic interactions are essential for removing oil droplets from rock substrates. Our work illustrates the impact of surface charge on the oil contact angle in an ideal system comprising silica, water, and dodecane; smaller contact angles are observed for more polar substrates. Modifying the polarity of the model silica surface allows for the observation of the creation of heteromolecule channels and the process of stripping crude oil while accounting for the impacts of water flow and different types of surfactant molecules.

A Space Expander of Laparoscopic Rectal Cancer Surgery for Overweight or Obese Patients.

Background/need: Laparoscopic rectal cancer surgery (LRCS) has become a preferred approach for its minimal invasion and fast postoperative recovery. But it is challenging for the tumors of the middle and lower rectum, especially for overweight or obese patients.

Methodology: We present a space expander of laparoscopic rectal cancer surgery, which is a simple tool to widen the perirectal space, as to facilitate the procedure of total mesorectal excision (TME) during the rectal cancer surgery.

Optical gain at 1.55 µm of Er(TMHD) complex doped polymer waveguides based on the intramolecular energy transfer effect.

Based on the intramolecular energy transfer mechanism between organic ligand TMHD (2, 2, 6, 6-tetramethyl-3, 5-heptanedione) and central Er ions, optical gains at 1.55 µm were demonstrated in three structures of polymer waveguides using complex Er(TMHD)-doped polymethylmethacrylate (PMMA) as the active material. With the excitation of two low-power UV light-emitting diodes (LEDs) instead of 980 or 1480 nm lasers, relative gains of 3.

Optical Amplification at 637 and 1067 nm Based on Organic Molecule AQ(PhDPA) and Nd Complex Codoped Polymer Waveguides.

Based on the molecular energy transfer mechanism, relative gains at 1067 and 637 nm wavelengths are achieved in thermally activated delayed fluorescence molecule AQ(PhDPA) and Nd complex with chelating phosphine oxide as ligands codoped polymer waveguides, with the excitation of low-power UV light-emitting diodes (LEDs) instead of traditional semiconductor lasers as pump sources. For AQ(PhDPA) -Nd(DBTTA) (DBFDPO) (DBTTA = dibenzotetrathienoacene, DBFDPO = 4,6-bis (diphenylphosphoryl) dibenzofuran) -codoped polymethylmethacrylate (PMMA), and AQ(PhDPA) -Nd(DBTTA) (FDPO) (FDPO = 9,9-bis (diphenylphosphorylphenyl) fluorene)-codoped PMMA polymers with a mass ratio of 1:4 respectively, when they are spin-coated as upper claddings, the relative gains of 2.2 and 1.

Self-Masked Aldehyde Inhibitors of Human Cathepsin L Are Potent Anti-CoV-2 Agents.

Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs.

An analysis of melanoma epidemic characteristics and distribution in the eastern Chinese city Ningbo from 2011 to 2018.

Background: Melanoma is a malignant tumor with poor prognosis and increasing global incidence. Little is known about the burden of melanoma in eastern Chinese cities, as the results of previous studies are inconsistent or unclear.

Methods: In this study, we collected incidence rate data from the Ningbo National Health Information Platform, diagnostic data from the Ningbo Clinicopathological Diagnosis Center, and other relevant data from the Ningbo Bureau of Statistics to evaluate temporal trends and geographic variation in melanoma incidence and to analyze the relationship between melanoma incidence and medical resource availability.

Dinitrosyl iron complexes (DNICs) as inhibitors of the SARS-CoV-2 main protease.

By repurposing DNICs designed for other medicinal purposes, the possibility of protease inhibition was investigated in silico using AutoDock 4.2.6 (AD4) and in vitro via a FRET protease assay.

Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases.

Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs.

A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and Monkey Cells.

Host-cell cysteine proteases play an essential role in the processing of the viral spike protein of SARS coronaviruses. K777, an irreversible, covalent inactivator of cysteine proteases that has recently completed phase 1 clinical trials, reduced SARS-CoV-2 viral infectivity in several host cells: Vero E6 (EC< 74 nM), HeLa/ACE2 (4 nM), Caco-2 (EC = 4.3 μM), and A549/ACE2 (<80 nM).

Tea polyphenols and Levofloxacin alleviate the lung injury of hepatopulmonary syndrome in common bile duct ligation rats through Endotoxin -TNF signaling.

Background & Aims: Hepatopulmonary syndrome (HPS) is characterized by pulmonary vasodilation and arterial blood oxygen desaturation in patients with chronic liver disease. Generally, common bile duct ligation (CBDL) rats are a suitable experimental model for studying hepatopulmonary syndrome. Our previous study demonstrated that endotoxin surges markedly, followed by bacterial translocation and the loss of liver immune function in all the stages of CBDL, thereby contributing to the pathogenesis of HPS.

A cysteine protease inhibitor blocks SARS-CoV-2 infection of human and monkey cells.

K777 is a di-peptide analog that contains an electrophilic vinyl-sulfone moiety and is a potent, covalent inactivator of cathepsins. Vero E6, HeLa/ACE2, Caco-2, A549/ACE2, and Calu-3, cells were exposed to SARS-CoV-2, and then treated with K777. K777 reduced viral infectivity with EC50 values of inhibition of viral infection of: 74 nM for Vero E6, <80 nM for A549/ACE2, and 4 nM for HeLa/ACE2 cells.

Isolated metachronous splenic multiple metastases after colon cancer surgery: A case report and literature review.

Background: Isolated splenic metastasis is a rare clinical entity. Multiple metastases in the spleen after radical colon resection in a patient who subsequently underwent a second local resection for isolated metachronous splenic metastasis are exceedingly rare.

Case Summary: We report a colon cancer patient who underwent laparoscopic radical colon resection 14 mo previously, and subsequently underwent a second local resection due to local recurrence detected by elevated serum carcinoembryonic antigen (CEA) and positron emission tomography (PET).

Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge.

Brown adipose tissue (BAT) is a specialized thermogenic organ in mammals. The ability of BAT mitochondria to generate heat in response to cold-challenge to maintain core body temperature is essential for organismal survival. While cold activated BAT mitochondrial biogenesis is recognized as critical for thermogenic adaptation, the contribution of mitochondrial quality control to this process remains unclear.

MiR-146a suppresses hepatocellular carcinoma by downregulating TRAF6.

MicroRNAs have been proven to play important roles in many biological processes such as cellular growth and differentiation, apoptosis, and modulation of host response to viral infection. In the present study, we find that the expression of miR-146a was decreased in hepatocellular carcinoma (HCC) tissues compared with corresponding adjacent tissues, and the expression level in HCC cell lines was lower than in a normal liver cell. Over-expression suppressed the proliferation and invasion of HCC cells.