Identification and validation of WDR5 WIN-site ligands via DNA-encoded chemical library screening.

WD repeat-containing protein 5 (WDR5) is a scaffolding protein involved in critical protein-protein interactions and a promising target for therapeutic development. Novel small-molecule ligands targeting WDR5 were identified using the DELopen platform, a free-access DNA-encoded chemical library (DEL) for academic research. Through off-DNA structure-activity relationship studies and photoaffinity labeling, two promising initial leads, DBL-6-13 and DBL-6-33, were identified as new binders of WDR5.

SARS-CoV-2 nsp13 suppresses hepatitis B virus replication by targeting cccDNA transcription.

Unlabelled: SARS-CoV-2 nonstructural protein 13 (nsp13) has been shown to selectively suppress the transcription of episomal DNA while sparing chromosomal DNA. Hepatitis B Virus (HBV) harbors covalently closed circular DNA (cccDNA), a form of viral episomal DNA found within infected hepatocyte nuclei. The persistence of cccDNA is the major cause of chronic HBV infection.

Ultrahigh-channel-count OAM mode conversion utilizing a hybrid few-mode fiber configuration.

We propose and demonstrate a hybrid few-mode fiber configuration (HFMFC) that enables ultrahigh-channel-count orbital angular momentum (OAM) mode conversion. The HFMFC consists of periodically twisted graded-index few-mode fiber segments and a step-index few-mode fiber segment. Our proposed HFMFC-based multichannel OAM mode converter (OAM-MC) offers an exceptionally high channel count in a wide bandwidth, with customizable channel spacing down to 50 GHz (∼0.

PROTAC-Mediated HDAC7 Protein Degradation Unveils Its Deacetylase-Independent Proinflammatory Function in Macrophages.

Class IIa histone deacetylases (Class IIa HDACs) play critical roles in regulating essential cellular metabolism and inflammatory pathways. However, dissecting the specific roles of each class IIa HDAC isoform is hindered by the pan-inhibitory effect of current inhibitors and a lack of tools to probe their functions beyond epigenetic regulation. In this study, a novel PROTAC-based compound B4 is developed, which selectively targets and degrades HDAC7, resulting in the effective attenuation of a specific set of proinflammatory cytokines in both lipopolysaccharide (LPS)-stimulated macrophages and a mouse model.

Identification of 5-Thiocyanatothiazol-2-amines Disrupting WDR5-MYC Protein-Protein Interactions.

amplification is frequently observed in approximately 50% of human cancers, rendering it a highly desired anticancer target. Given the challenge of direct pharmacological inhibiting of MYC, impairing the interaction of MYC and its key cofactor WDR5 has been proposed as a promising strategy for MYC-driven cancer treatment. Herein, we report the discovery of 5-thiocyanatothiazol-2-amines that disrupt the WDR5-MYC interaction.

Generation of optical vortex beams with bandwidth exceeding 550 nm using a helical fiber needle exhibiting strong mode coupling.

A strong-coupling helical fiber needle (HFN) is proposed and demonstrated for the realization of bandwidth-enhanced broadband optical vortex beam (OVB) generation. The HFN is based on a single mode fiber and operates at the dispersion-turning-point (DTP) of the lowest radial order of the cladding mode (i.e.

Design, synthesis, and antitumor activity evaluation of potent fourth-generation EGFR inhibitors for treatment of Osimertinib resistant non-small cell lung cancer (NSCLC).

Epidermal growth factor receptor (EGFR) is one of the most studied drug targets for treating non-small-cell lung cancer (NSCLC). However, there are no approved inhibitors for the C797S resistance mutation caused by the third-generation EGFR inhibitor (Osimertinib). Therefore, the development of fourth-generation EGFR inhibitors is urgent.

Epidemiological and Clinical Characteristics of Neonatal Infection.

Purpose: To understand the epidemiology and clinical features of (UU) infection in hospitalized neonates due to vertical transmission from mother to child.

Methods: Respiratory secretions were collected from neonates hospitalized in the neonatology department of the Maternal and Child Health Hospital of Hubei Province from July 2020 to June 2022, and PCR was used to detect UU-DNA in respiratory secretions. The neonates were divided into UU-positive and UU-negative groups, the epidemiological and clinical characteristics of two groups, were statistically analyzed.

Association between Gut Microbiota and Biological Aging: A Two-Sample Mendelian Randomization Study.

Recent observational studies revealed an association between gut microbiota and aging, but whether gut microbiota are causally associated with the aging process remains unknown. We used a two-sample Mendelian randomization approach to investigate the causal association between gut microbiota and biological age acceleration using the largest available gut microbiota GWAS summary data from the MiBioGen consortium and GWAS data on biological age acceleration. We further conducted sensitivity analysis using MR-PRESSO, MR-Egger regression, Cochran Q test, and reverse MR analysis.

Transcriptomic Signature of 3D Hierarchical Porous Chip Enriched Exosomes for Early Detection and Progression Monitoring of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers.

HBV promotes its replication by up-regulating RAD51C gene expression.

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), pegylated-interferon-α(PEG-IFNα) and long-term nucleos(t)ide analogs (NUCs) are mainly drugs used to treat HBV infection, but the effectiveness is unsatisfactory in different populations, the exploration of novel therapeutic approaches is necessary. RAD51C is associated with DNA damage repair and plays an important role in the development and progression of tumors. Early cDNA microarray results showed that RAD51C expression was significantly increased in HBV-infected HCC cells, however, the relationship between HBV infection and abnormal expression of RAD51C has not been reported.

On-demand flat-top wideband OAM mode converter based on a cladding-etched helical fiber grating.

A new method enabling to provide an on-demand flat-top wideband orbital angular momentum (OAM) mode converter is proposed and experimentally demonstrated, which is based on utilization of a cladding-etched helical long-period fiber grating (CEHLPG). By appropriately selecting the grating period and precisely controlling the diameter of the CEHLPG in-situ, both the radial order and central wavelength of the flat-top band for the generated OAM mode can be flexibly tailored according to specific requirements. As typical examples, the first azimuthal order OAM modes with a flat-top bandwidth of 95 nm at -20 dB, a central operating wavelength of ∼1500 nm, and the radial-orders of 9, 8, 5, and 2, respectively, have been demonstrated consecutively.

STAT3 palmitoylation initiates a positive feedback loop that promotes the malignancy of hepatocellular carcinoma cells in mice.

Constitutive activation of the transcription factor STAT3 (signal transducer and activator of transcription 3) contributes to the malignancy of many cancers such as hepatocellular carcinoma (HCC) and is associated with poor prognosis. STAT3 activity is increased by the reversible palmitoylation of Cys by the palmitoyltransferase DHHC7 (encoded by ). Here, we investigated the consequences of S-palmitoylation of STAT3 in HCC.

Corrigendum: The prospective outcome of the Monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology.

[This corrects the article DOI: 10.3389/fcimb.2023.

Acoustic quasi-periodic bioassembly based diverse stem cell arrangements for differentiation guidance.

Arrangement patterns and geometric cues have been demonstrated to influence cell function and fate, which calls for efficient and versatile cell patterning techniques. Despite constant achievements that mainly focus on individual cells and uniform cell patterns, simultaneously constructing cellular arrangements with diverse patterns and positional relationships in a flexible and contact-free manner remains a challenge. Here, stem cell arrangements possessing multiple geometries and structures are proposed based on powerful and diverse pattern-building capabilities of quasi-periodic acoustic fields, with advantages of rich patterns and structures and flexibility in structure modulation.

Full C-band covered and DWDM channelized high channel-count all-fiber orbital-angular-momentum mode generator based on the fiber gratings.

To generate the orbital-angular-momentum (OAM) modes at multiple wavelengths, which exactly fit with the dense-wavelength-division-multiplex (DWDM) channel grids, is important to the DWDM-based OAM mode-division-multiplex (MDM) fiber communication system. In this study, a full C-band covered and DWDM channelized OAM mode generator is firstly proposed and experimentally demonstrated, which is realized especially by using a broadband helical long-period fiber grating (HLPG) combined with a phase-only sampled multichannel fiber Bragg grating (MFBG). As a proof-of-concept example, the DWDM channelized two complementary 51-channel OAM mode generators have been successfully demonstrated, each of which has a channel spacing of 100 GHz (∼0.

Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: a population-based study.

Background: The Systemic Immune-Inflammation Index (SII) is a quantitative measurement of the systemic immune-inflammatory response in the human body. The SII has been shown to have prognostic value in various clinical settings, including critical illness, sepsis, and cancer. Its role in chronic obstructive pulmonary disease (COPD) remains unclear and requires further investigation.

The prospective outcome of the monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology.

A new threat to global health re-emerged with monkeypox's advent in early 2022. As of November 10, 2022, nearly 80,000 confirmed cases had been reported worldwide, with most of them coming from places where the disease is not common. There were 53 fatalities, with 40 occurring in areas that had never before recorded monkeypox and the remaining 13 appearing in the regions that had previously reported the disease.

Valve-Adjustable Optofluidic Bio-Imaging Platform for Progressive Stenosis Investigation.

The clinical evidence has proven that valvular stenosis is closely related to many vascular diseases, which attracts great academic attention to the corresponding pathological mechanisms. The investigation is expected to benefit from the further development of an in vitro model that is tunable for bio-mimicking progressive valvular stenosis and enables accurate optical recognition in complex blood flow. Here, we develop a valve-adjustable optofluidic bio-imaging recognition platform to fulfill it.

β-Glucan Induces Training Immunity to Promote Antiviral Activity by Activating TBK1.

Many studies have shown that β-glucan induces a trained immune phenotype in innate immune cells to defend against bacterial and fungal infections. The specific mechanism involves cellular metabolism and epigenetic reprogramming. However, it is unclear whether β-glucan plays a role in antiviral infection.

Human papillomavirus genotypic characteristics of 60,685 subjects under age-expansion vaccination of the nine-valent human papillomavirus vaccine: A cross-sectional study.

Background: Human papillomavirus (HPV) vaccination is a key initiative to promote the WHO global strategy to accelerate the elimination of cervical cancer, and this study aimed to investigate the current status of HPV infection and genotypic characteristics of the population under the impact of age-expansion of nine-valent HPV vaccination policy in China.

Methods: The clinical data of 60,685 subjects who were admitted in the Renmin Hospital of Wuhan University and underwent HPV genotyping from January 2017 to October 2022 were retrospectively analyzed.

Results: The total number of positive HPV genotyping in the included population was 10,303, with a positivity rate of 17.