Remdesivir alleviates skin fibrosis by suppressing TGF-β1 signaling pathway.

Fibrotic skin diseases, such as keloids, are pathological results of aberrant tissue healing and are characterized by overgrowth of dermal fibroblasts. Remdesivir (RD), an antiviral drug, has been reported to have pharmacological activities in a wide range of fibrotic diseases. However, whether RD function on skin fibrosis remains unclear.

High luminous efficiency and high saturation threshold in highly transparent LuAG:Ce phosphor ceramics for laser diodes lighting.

LuAlO:Ce (LuAG:Ce) phosphor ceramics (PCs) with the excellent thermal stability and high saturation threshold are considered as the best green-fluorescent converters for high-power laser diodes (LDs) lighting. In this study, the effects of sintering additives and sintering processes on the transmittance and microstructure of LuAG:Ce PCs were systematically studied, and the luminescence performance of ceramics with different transmittance was compared. LuAG:Ce PCs with the transmittance of 80% (@800 nm, 1.

High luminous efficiency and excellent thermal performance in rod-shaped YAG:Ce phosphor ceramics for laser lighting.

High power and high brightness laser lighting puts forward new requirements for phosphor converters such as high luminous efficiency, high thermal conductivity and high saturation threshold due to the severe thermal effect. The structure design of phosphor converters is proposed as what we believe to be a novel strategy for less heat production and more heat conduction. In this work, the rod-shaped YAG:Ce phosphor ceramics (PCs) and disc-shaped YAG:Ce PCs as control group were fabricated by the gel casting and vacuum sintering, to comparatively study the luminescence performance for LD lighting, on the premise that the total number of transverse Ce ions and the volume of samples from two comparison groups were same.

Passive microfluidic devices for cell separation.

The separation of specific cell populations is instrumental in gaining insights into cellular processes, elucidating disease mechanisms, and advancing applications in tissue engineering, regenerative medicine, diagnostics, and cell therapies. Microfluidic methods for cell separation have propelled the field forward, benefitting from miniaturization, advanced fabrication technologies, a profound understanding of fluid dynamics governing particle separation mechanisms, and a surge in interdisciplinary investigations focused on diverse applications. Cell separation methodologies can be categorized according to their underlying separation mechanisms.

Barcode-structured YAG:Ce/YAG:Ce,Mn ceramic phosphors for variable CCT and high CRI LED/LD lighting.

Ceramic phosphors are widely considered the next-generation phosphor material for white LED/LD lighting, and a wide spectrum is a key factor in improving the CRI of lighting sources. In this paper, a novel, to our knowledge, barcode-structured YAG:Ce/YAG:Ce,Mn ceramic phosphor was designed and fabricated. The lighting sources with the CRI value of 73.

Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study.

Introduction: In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients.

Patients And Methods: In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.

Optical properties and energy transfer performances in high quality Cr,Nd: YAG transparent laser ceramics for solar pumped lasers.

Realizing a high solar light conversion magnitude in Cr,Nd: YAG transparent ceramic is crucial to its applications in solar pumped solid state lasers. In this study, high quality Cr,Nd:YAG transparent laser ceramics with homogeneous microstructure and theoretical transmittance were fabricated, and an efficient laser oscillation of watt-level was realized by pumping ceramic at 808 nm. There were no any characteristic absorptions corresponding to Cr or Cr ions detected, even when the Cr ion doping concentration reached 0.

Discovery of Highly Potent and Selective IRAK1 Degraders to Probe Scaffolding Functions of IRAK1 in ABC DLBCL.

MyD88 gene mutation has been identified as one of the most prevalent driver mutations in the activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL). The published literature suggests that interleukin-1 receptor-associated kinase 1 (IRAK1) is an essential gene for ABC DLBCL harboring MyD88 mutation. Importantly, the scaffolding function of IRAK1, rather than its kinase activity, is required for tumor cell survival.

Broadband emission GdScAlO:Ce transparent ceramics with a high color rendering index for high-power white LEDs/LDs.

The discovery of single structure Ce doped garnet transparent ceramics (TCs) with a broad full width at half maximum (FWHM) is essential to realize a high CRI for high-power white light emitting diodes (LEDs) and laser diodes (LDs). In this work, by utilizing the ion substitution engineering strategy, pure phase GdScAlO:Ce (GSAG:Ce) TC with a broad FWHM of 132.4 nm and a high CRI value of 80.

Histone deacetylase SIR2 in Toxoplasma gondii modulates functions of murine macrophages in vitro and protects mice against acute toxoplasmosis in vivo.

Silent information regulator 2 (SIR2) in histone deacetylase (HDAC) is particularly conserved and widely expressed in all eukaryotic cells. HDAC is a crucial post-translational modification protein regulating gene expression. In the present study, a Toxoplasma gondii (T.

Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study.

Background: Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL.

Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption.

In multiple myeloma, inflammatory and anti-viral pathways promote disease progression and cancer stem cell generation. Using diverse pre-clinical models, we investigated the role of interferon regulatory factor 4 (IRF4) in myeloma progenitor regeneration. In a patient-derived xenograft model that recapitulates IRF4 pathway activation in human myeloma, we test the effects of IRF4 antisense oligonucleotides (ASOs) and identify a lead agent for clinical development (ION251).

Modulation Effects of Histone H2A1 on Murine Macrophages and Encapsulation with Polymer as a Vaccine Candidate.

() is the most common zoonotic protozoa and has infected about one-third of the population worldwide. Recombinant epitopes encapsulated in nanospheres have advantages over traditional vaccines. For an efficient delivery system, poly (DL-lactide-co-glycolide) (PLGA) and chitosan are the most frequently used biodegradable polymeric nanospheres with strong safety profiles.

Assessing IRAK4 Functions in ABC DLBCL by IRAK4 Kinase Inhibition and Protein Degradation.

The interleukin-1 receptor-activated kinase 4 (IRAK4) belongs to the IRAK family of serine/threonine kinases and plays a central role in the innate immune response. However, the function of IRAK4 in tumor growth and progression remains elusive. Here we sought to determine the enzymatic and scaffolding functions of IRAK4 in activated B-cell-like diffuse large B cell lymphoma (ABC DLBCL).

Interferon regulatory factor 4 as a therapeutic target in adult T-cell leukemia lymphoma.

Background: Adult T-cell leukemia lymphoma (ATLL) is a chemotherapy-resistant malignancy with a median survival of less than one year that will afflict between one hundred thousand and one million individuals worldwide who are currently infected with human T-cell leukemia virus type 1. Recurrent somatic mutations in host genes have exposed the T-cell receptor pathway through nuclear factor κB to interferon regulatory factor 4 (IRF4) as an essential driver for this malignancy. We sought to determine if IRF4 represents a therapeutic target for ATLL and to identify downstream effectors and biomarkers of IRF4 signaling in vivo.

Changes in Measles Seroprevalence in China After the Launch of Two Provincial Supplementary Immunization Activities During 2009 to 2013.

Background: Supplementary immunization activities (SIAs) have been demonstrated being effective in reducing measles incidence within a short period of time in China, but the effects are short-lived if there is no follow-up SIA with high routine immunization coverage.

Objectives: To assess the change in measles seroprevalence from 2009 to 2013 after the launch of 2 large-scale SIAs within the period.

Methods: Three population-based cross-sectional serologic surveys of measles antibodies were conducted in 2009, 2011 and 2013 in Zhejiang, a province in eastern China, with serologic samples collected from 1541, 896 and 1474 subjects, respectively.

Early Waning of Maternal Measles Antibodies in Infants in Zhejiang Province, China: A Comparison of Two Cross-Sectional Serosurveys.

In China, children aged <8 months, who were expected to be protected by maternal antibodies before receiving the first dose of measles vaccine, were the age group with the greatest risk of infection in recent years. In this study, we evaluated whether infants yet to be age-eligible for measles vaccine had a sufficient seropositive level of maternal measles antibodies in 2009 and 2013. Blood samples were collected from infants aged <8 months through population-based serological surveys conducted in Zhejiang, China.

Enhanced Potency of GalNAc-Conjugated Antisense Oligonucleotides in Hepatocellular Cancer Models.

Antisense oligonucleotides (ASOs) are a novel therapeutic approach to target difficult-to-drug protein classes by targeting their corresponding mRNAs. Significantly enhanced ASO activity has been achieved by the targeted delivery of ASOs to selected tissues. One example is the targeted delivery of ASOs to hepatocytes, achieved with N-acetylgalactosamine (GalNAc) conjugation to ASO, which results in selective uptake by asialoglycoprotein receptor (ASGR).

An HK2 Antisense Oligonucleotide Induces Synthetic Lethality in HK1HK2 Multiple Myeloma.

Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1HK2 cancers, HK1HK2 cancer subsets are sensitive to cytostasis induced by HK2 knockdown and are also sensitive to synthetic lethality in response to the combination of HK2 knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1HK2.

STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial.

Background: The Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival.

Antisense STAT3 inhibitor decreases viability of myelodysplastic and leukemic stem cells.

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Transcriptomic analysis of stem and progenitor populations in MDS and AML demonstrated overexpression of STAT3 that was validated in an independent cohort. STAT3 overexpression was predictive of a shorter survival and worse clinical features in a large MDS cohort.

Hopes and challenges for giant panda conservation under climate change in the Qinling Mountains of China.

One way that climate change will impact animal distributions is by altering habitat suitability and habitat fragmentation. Understanding the impacts of climate change on currently threatened species is of immediate importance because complex conservation planning will be required. Here, we mapped changes to the distribution, suitability, and fragmentation of giant panda habitat under climate change and quantified the direction and elevation of habitat shift and fragmentation patterns.

Energy level systems and transitions of Ho:LuAG laser resonantly pumped by a narrow line-width Tm fiber laser.

We presented a Ho:LuAG ceramic laser in-band pumped by a narrow emission line-width Tm fiber laser at 1907 nm. All of potential transitions between 5I7 and 5I8 manifold were discussed to form the Ho's in-band-pump energy level systems, which were not described in details earlier. For the emission band centered at ~2095 nm, both laser absorption and emission transition separately consisted of two groups were first analyzed and observed.