Role of calcineurin in regulating renal potassium (K+) excretion: Mechanisms of calcineurin inhibitor-induced hyperkalemia.

Calcineurin, protein phosphatase 2B (PP2B) or protein phosphatase 3 (PP3), is a calcium-dependent serine/threonine protein phosphatase. Calcineurin is widely expressed in the kidney and regulates renal Na+ and K+ transport. In the thick ascending limb, calcineurin plays a role in inhibiting NKCC2 function by promoting the dephosphorylation of the cotransporter and an intracellular sorting receptor, called sorting-related-receptor-with-A-type repeats (SORLA), is involved in modulating the effect of calcineurin on NKCC2. Calcineurin also participates in regulating thiazide-sensitive NaCl-cotransporter (NCC) in the distal convoluted tubule. The mechanisms by which calcineurin regulates NCC include directly dephosphorylation of NCC, regulating Kelch-like-3/CUL3 E3 ubiquitin-ligase complex, which is responsible for WNK (with-no-lysin-kinases) ubiquitination, and inhibiting Kir4.1/Kir5.1, which determines NCC expression/activity. Finally, calcineurin is also involved in regulating ROMK (Kir1.1) channels in the cortical collecting duct and Cyp11 2 expression in adrenal zona glomerulosa. In summary, calcineurin is involved in the regulation of NKCC2, NCC, and inwardly rectifying K+ channels in the kidney, and it also plays a role in modulating aldosterone synthesis in adrenal gland, which regulates epithelial-Na+-channel expression/activity. Thus, application of calcineurin inhibitors (CNIs) is expected to abrupt calcineurin-mediated regulation of transepithelial Na+ and K+ transport in the kidney. Consequently, CNIs cause hypertension, compromise renal K+ excretion, and induce hyperkalemia.

A Novel Effect of Id2 in Microglia TNFα Regulation.

Microglia are the most important immune cells in the central nervous system (CNS), which can defend against external pathogens and stimuli. Dysregulation of microglia releases excessive proinflammatory cytokines and leads to neuroinflammation, which is fundamental to the pathophysiology of multiple neurological diseases. However, the molecular mechanisms underlying the regulation of proinflammatory cytokines in microglia are still not well-understood. Here, we identified that inhibitor of DNA binding protein 2 (Id2) was a negative regulator of tumor necrosis factor-α (TNFα) in cultured microglia. Knockdown of Id2 significantly increased the expression of TNFα in microglia, while overexpression of Id2 inhibited TNFα expression. Furthermore, by interacting with the p65 subunit of nuclear factor kappa-B (NF-κB), Id2 suppressed the transcription activation of NF-κB and inhibited TNFα expression. Interestingly, in lipopolysaccharides (LPS)-treated microglia, Id2 increased and underwent a cytoplasmic relocation. Immunoprecipitation and immunostaining results showed that by binding to the LIM domain of Id2, a scaffold protein PDZ and LIM 5 (PDLIM5) involved in the Id2 cytoplasmic relocation, which inactivated Id2 and resulted in higher TNFα expression in LPS-treated microglia. Collectively, our data delineate a novel effect of Id2 on TNFα regulation in microglia, which may shed a light on the proinflammatory cytokines regulating in microglia associated neuroimmune disorders.

Evolutionary Diversity of Coxsackievirus A6 Causing Severe Hand, Foot, and Mouth Disease - China, 2012-2023.

Introduction: Coxsackievirus A6 (CVA6) has emerged as a significant pathogen responsible for severe cases of hand, foot, and mouth disease (HFMD). This study aims to delineate the demographic characteristics and analyze the viral evolution of severe HFMD associated with CVA6, thereby assisting in its surveillance and management. Methods: In this investigation, 74 strains of CVA6 were isolated from samples collected from severe HFMD cases between 2012 and 2023. The VP1 gene sequences of CVA6 were amplified and analyzed to assess population historical dynamics and evolutionary characteristics using BEAST, DnaSP6, and PopART. Results: A significant portion (94.4%) of severe CVA6-associated HFMD cases (51 out of 54, with 20 lacking age information) were children under 5 years old. Among the 74 CVA6 strains analyzed, 72 belonged to the D3a sub-genotype, while only two strains were D2 sub-genotype. The average genetic distance between VP1 sequences prior to 2015 was 0.027, which increased to 0.051 when compared to sequences post-2015. Historical population dynamics analysis indicated three significant population expansions of severe CVA6-associated HFMD during 2012-2013, 2013-2014, and 2019-2020, resulting in the formation of 65 distinct haplotypes. Consistent with the MCC tree findings, transitioning between regional haplotypes required multiple base substitutions, showcasing an increase in population diversity during the evolutionary process (from 14 haplotypes in 2013 to 55 haplotypes over the subsequent decade). Conclusions: CVA6, associated with severe HFMD, is evolving and presents a risk of outbreak occurrence. Thus, enhanced surveillance of severe HFMD is imperative.

Seasonal and Genetic Characteristics of Human Metapneumovirus Circulating - Henan Province, China, 2017-2023.

Introduction: This study examines the seasonal and genetic characteristics of human metapneumovirus (HMPV) in Henan from 2017 to 2023. Methods: Samples from patients with acute respiratory infection (ARI) testing positive for HMPV were subjected to real-time reverse transcription polymerase chain reaction The G gene was amplified and sequenced from these samples for epidemiological and phylogenetic analysis. Results: We enrolled 2,707 ARI patients from October 2017 to March 2023, finding an HMPV positivity rate of 6.17% (167/2,707). Children under five exhibited the highest infection rate at 7.78% (138/1,774). The 2018 and 2019 HMPV outbreaks predominantly occurred in spring (March to May), with peak positivity rates of 31.11% in May 2018 and 19.57% in May 2019. A notable increase occurred in November 2020, when positivity reached a historic high of 42.11%, continuing until January 2021. From February 2021 through March 2023, no significant seasonal peaks were observed, with rates ranging from 0% to 8.70%. Out of 81 G gene sequences analyzed, 46.91% (38/81) were identified as subtype A (A2c: 45.67%, 37/81; A2b: 1.23%, 1/81) and 53.09% (43/81) as subtype B (B1: 9.88%, 8/81; B2: 43.21%, 35/81). Notably, an AAABBA switch pattern was observed in HMPV subtypes. The dominant strains were A2c111nt-dup in subtype A and B2 in subtype B. Conclusions: Six years of surveillance in Henan Province has detailed the seasonal and genetic dynamics of HMPV, contributing valuable insights for the control and prevention of HMPV infections in China. These findings support the development of targeted HMPV vaccines and immunization strategies.

Broadband mid-infrared photodetectors utilizing two-dimensional van der Waals heterostructures with parallel-stacked pn junctions.

Optimizing the width of depletion region is a key consideration in designing high performance photovoltaic photodetectors, as the electron-hole pairs generated outside the depletion region cannot be effectively separated, leading to a negligible contribution to the overall photocurrent. However, currently reported photovoltaic mid-infrared photodetectors based on two-dimensional heterostructures usually adopt a single pn junction configuration, where the depletion region width is not maximally optimized. Here, we demonstrate the construction of a high performance broadband mid-infrared photodetector based on a MoS2/b-AsP/MoS2 npn van der Waals heterostructure. The npn heterojunction can be equivalently represented as two parallel-stacked pn junctions, effectively increasing the thickness of the depletion region. Consequently, the npn device shows a high detectivity of 1.3×1010 cmHz1/2W-1 at the mid-infrared wavelength, which is significantly improved compared with its single pn junction counterpart. Moreover, it exhibits a fast response speed of 12 µs, and a broadband detection capability ranging from visible to mid-infrared wavelengths.

In-Situ Self-Reconfiguration Induced Multifunctional Triple-Gradient Artificial Interfacial Layer towards Long-Life Zn-Metal Anodes.

Aqueous Zn-ion batteries featuring with intrinsic safety and low cost are highly desirable for large-scale energy storage, but the unstable Zn-metal anode resulting from uncontrollable dendrite growth and grievous hydrogen evolution reaction (HER) shortens their cycle life. Herein, a feasible in-situ self-reconfiguration strategy is developed to generate triple-gradient poly(diallyldimethylammonium) bis(trifluoromethanesulfonyl)imide (PDDA-TFSI)-Zn5(OH)8Cl2·H2O-Sn (PT-ZHC-Sn) artificial layer. The resulting triple-gradient interface consists of the spherical top layer PT with cation confinement and H2O inhibition, the dense intermediate layer ZHC nanosheet with Zn2+ conduction and electron shielding, and the bottom layer Znophilic Sn metal. The well-designed triple-gradient artificial interfacial layer synergistically facilitates rapid Zn2+ diffusion to regulate uniform Zn deposition and accelerates the desolvation process while suppressing HER. Consequently, the PT-ZHC-Sn@Zn symmetric cell achieves an ultralong lifespan over 6500 h at 0.5 mA cm-2 for 0.5 mAh cm-2. Furthermore, a full battery coupling with MnO2 cathode exhibits a 17.2% increase in capacity retention compared with bare Zn anode after 1000 cycles. The in-situ self-reconfiguration strategy is also applied to prepare triple-gradient PT-ZHC-In, and the assembled Zn//Cu cell operates steadily for over 8400 h while maintaining Coulombic efficiency of 99.6%. This work paves the way to designing multicomponent gradient interface for stable Zn-metal anodes. This article is protected by copyright. All rights reserved.

Research Progress of Baihe Gujin Decoction in the Treatment of Lung Cancer.

Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and ß-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.

Validated enhancement and temperature modulated absorbance of a WS2 monolayer based on a planar structure.

Transition-metal dichalcogenides (TMDCs), as emerging optoelectronic materials, necessitate the establishment of an experimentally viable system to study their interaction with light. In this study, we propose and analyze a WS2/PMMA/Ag planar Fabry-Perot (F-P) cavity, enabling the direct experimental measurement of WS2 absorbance. By optimizing the structure, the absorbance of A exciton of WS2 up to 0.546 can be experimentally achieved, which matches well with the theoretical calculations. Through temperature and thermal expansion strain induced by temperature, the absorbance of the A exciton can be tuned in situ. Furthermore, temperature-dependent photocurrent measurements confirmed the consistent absorbance of the A exciton under varying temperatures. This WS2/PMMA/Ag planar structure provides a straightforward and practical platform for investigating light interaction in TMDCs, laying a solid foundation for future developments of TMDC-based optoelectronic devices.

Hinokione: an abietene diterpene with pancreatic ß cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara.

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into ß cells, thereby promoting the regeneration of pancreatic ß cells.

Distribution characteristics of gastric mucosal colonizing microorganisms in different glandular regions of Bactrian camels and their relationship with local mucosal immunity.

Bactrian camels inhabiting desert and semi-desert regions of China are valuable animal models for studying adaptation to desert environments and heat stress. In this study, 16S rRNA technology was employed to investigate the distribution characteristics and differences of mucosal microorganisms in the anterior gland area, posterior gland area, third gland area, cardia gland area, gastric fundic gland area and pyloric gland area of 5-peak adult healthy Bactrian camels. We aimed to explore the possible reasons for the observed microbial distribution from the aspects of histological structure and mucosal immunity. Bacteroides and Fibrobacteria accounted for 59.54% and 3.22% in the gland area, respectively, and 52.37% and 1.49% in the wrinkled stomach gland area, respectively. The gland area showed higher abundance of Bacteroides and Fibrobacteria than the wrinkled stomach gland area. Additionally, the anterior gland area, posterior gland area, third gland area, and cardia gland area of Bactrian camels mainly secreted acidic mucus, while the gastric fundic gland area mainly secreted neutral mucus and the pyloric region mainly secreted a mixture of acidic and neutral mucus. The results of immunohistochemistry techniques demonstrated that the number of IgA+ cells in the anterior glandular area, posterior glandular area, third glandular area, and cardia gland area was significantly higher than that in the fundic and pyloric gland area (p < 0.05), and the difference in IgA+ between the fundic and pyloric gland area was not significant (p > 0.05). The study revealed a large number of bacteria that can digest and degrade cellulose on the mucosa of the gastric gland area of Bactrian camels. The distribution of IgA+ cells, the structure of the mucosal tissue in the glandular region, and the composition of the mucus secreted on its surface may have a crucial influence on microbial fixation and differential distribution.

Enantioselective α-Trifluoromethylthiolation of Carbonyl Compounds with AgSCF3 and Trichloroisocyanuric Acid.

We successfully developed an enantioselective trifluoromethylthiolation of structurally diverse carbonyl compounds. Trichloroisocyanuric acid and AgSCF3 were employed to generate active electrophilic trifluoromethylthio species in situ for asymmetric C-SCF3 bond formation. A broad variety of chiral SCF3-carbon nucleophiles (pyrazolones, ß-keto esters, and ß-keto amides) were obtained in excellent yields with high enantioselectivities (up to 92% ee) by Cinchona alkaloid derived squaramide catalysts. The reaction exhibits high efficiency, good enantioselectivity, and high functional group tolerance, which provided a novel and efficient way for asymmetric synthesis of trifluoromethylthiolated carbonyl compounds.

Adhesion between EVs and tumor cells facilitated EV-encapsulated doxorubicin delivery via ICAM1.

Doxorubicin (Dox) is an anti-tumor drug with a broad spectrum, whereas the cardiotoxicity limits its further application. In clinical settings, liposome delivery vehicles are used to reduce Dox cardiotoxicity. Here, we substitute extracellular vesicles (EVs) for liposomes and deeply investigate the mechanism for EV-encapsulated Dox delivery. The results demonstrate that EVs dramatically increase import efficiency and anti-tumor effects of Dox in vitro and in vivo, and the efficiency increase benefits from its unique entry pattern. Dox-loading EVs repeat a "kiss-and-run" motion before EVs internalization. Once EVs touch the cell membrane, Dox disassociates from EVs and directly enters the cytoplasm, leading to higher and faster Dox import than single Dox. This unique entry pattern makes the adhesion between EVs and cell membrane rather than the total amount of EV internalization the key factor for regulating the Dox import. Furthermore, we recognize ICAM1 as the molecule mediating the adhesion between EVs and cell membranes. Interestingly, EV-encapsulated Dox can induce ICAM1 expression by irritating IFN-γ and TNF-α secretion in TME, thereby increasing tumor targeting of Dox-loading EVs. Altogether, EVs and EV-encapsulated Dox synergize via ICAM1, which collectively enhances the curative effects for tumor treatment.

Effect of Process Parameters on Welding Residual Stress of 316L Stainless Steel Pipe.

316L stainless steel pipes are widely used in the storage and transportation of low-temperature media due to their excellent low-temperature mechanical properties and corrosion resistance. However, due to their low thermal conductivity and large coefficient of linear expansion, they often lead to significant welding residual tensile stress and thermal cracks in the weld seam. This also poses many challenges for their secure and reliable applications. In order to effectively control the crack defects caused by stress concentration near the heat-affected zone of the weld, this paper establishes a thermal elastoplastic three-dimensional finite element (FE) model, constructs a welding heat source, and simulates and studies the influence of process parameters on the residual stress around the pipeline circumference and axial direction in the heat-affected zone. Comparison and verification were conducted using simulation and experimental methods, respectively, proving the rationality of the finite element model establishment. The axial and circumferential residual stress distribution obtained by the simulation method did not have an average deviation of more than 30 MPa from the numerical values obtained by the experimental method. This study also considers the effects of welding energy, welding speed, and welding start position on the pipe's circumferential and axial residual stress laws. The results indicate that changes in welding energy and welding speed have almost no effect on the longitudinal residual stress but have a more significant effect on the transverse residual stress. The maximum transverse residual stress is reached at a welding energy of 1007.4~859.3 J/mm and a welding speed of 6.6 mm/s. Various interlayer arc-striking deflection angles can impact the cyclic phase angle of the transverse residual stress distribution in the seam center, but they do not alter its cyclic pattern. They do influence the amplitude and distribution of the longitudinal residual stress along the circumference. The residual stress distribution on the surface of the pipe fitting is homogenized and improved at 120°.

DIPAN: Detecting personalized intronic polyadenylation derived neoantigens from RNA sequencing data.

Intronic polyadenylation (IPA) refers to a particular type of alternative polyadenylation where a gene makes use of a polyadenylation site located within its introns. Aberrant IPA events have been observed in various types of cancer. IPA can produce noncoding transcripts or truncated protein-coding transcripts with altered coding sequences in the resulting protein product. Therefore, IPA events hold the potential to act as a reservoir of tumor neoantigens. Here, we developed a computational method termed DIPAN, which incorporates IPA detection, protein fragmentation, and MHC binding prediction to predict IPA-derived neoantigens. Utilizing RNA-seq from breast cancer cell lines and ovarian cancer clinical samples, we demonstrated the significant contribution of IPA events to the neoantigen repertoire. Through mass spectrometry immunopeptidome analysis, we further illustrated the processing and presentation of IPA-derived neoantigens on the surface of cancer cells. While most IPA-derived neoantigens are sample-specific, shared neoantigens were identified in both cancer cell lines and clinical samples. Furthermore, we demonstrated an association between IPA-derived neoantigen burden and overall survival in cancer patients.

A whole-slide foundation model for digital pathology from real-world data.

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1-3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.

mTORc2 in Distal-Convoluted-Tubule and Renal K+-Excretion during High Dietary K+ Intake.

BACKGROUND: Renal mTORc2 plays a role in regulating renal K+-excretion (renal-EK) and K+-homeostasis. Inhibition of renal mTORc2 caused hyperkalemia due to suppressing epithelial-Na+-channel (ENaC) and ROMK (Kir1.1) in the collecting duct. We now explore whether mTORc2 of DCT regulates basolateral Kir4.1/Kir5.1, NCC and renal-EK. METHODS: We used patch-clamp-technique to examine basolateral Kir4.1/Kir5.1 in early-DCT, immunoblotting and immunofluorescence to examine NCC expression and in vivo measurement of urinary K+-excretion to determine baseline renal-EK in the mice treated with mTORc2-inhibitor and in DCT-specific Rapamycin-Insensitive-Companion- of-mTOR knockout (DCT-RICTOR-KO) mice. RESULTS: Inhibition of mTORc2 with AZD8055 abolished high-K+-induced inhibition of Kir4.1/Kir5.1 in DCT, high-K+-induced depolarization of DCT membrane and high-K+-induced suppression of pNCC expression. AZD8055 stimulated the 40-pS-inwardly-rectifying-K+ channel (Kir4.1/Kir5.1-heterotetramer) in early-DCT in the mice on overnight-high-K+, this effect was absent in the presence of PKC-inhibitor which also stimulated Kir4.1/Kir5.1. AZD8055-treatment decreased renal-EK in animals on overnight-high-K+. Deletion of RICTOR in the DCT increased the Kir4.1/Kir5.1-mediated K+-currents, hyperpolarized DCT membrane and increased the expression of pWNK4 and pNCC. Renal-EK was lower and plasma-K+ was higher in DCT-RICTOR-KO mice than corresponding control mice. Also, overnight-high-K+ did not inhibit Kir4.1/Kir5.1 activity in the DCT and failed to inhibit the expression of pNCC in DCT-RICTOR-KO mice. Overnight-high-K+ stimulated renal-EK in control mice, but this effect was attenuated in DCT-RICTOR-KO mice. Thus, overnight-high-K+ induced hyperkalemia in DCT-RICTOR-KO mice but not in control mice. CONCLUSIONS: mTORc2 of the DCT inhibits Kir4.1/Kir5.1 activity and NCC expression, and stimulates renal-EK during high-K+-intake.

Age-dependent distribution of IgA and IgG antibody-secreting cells in the pharyngeal tonsil of the Bactrian camel.

The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.

Dynamics and Internal Structure Evolution during the Glass Transition of the Ethylene-Cyclic Olefin Copolymers: A Molecular Dynamics Simulation.

Amorphous ethylene-cyclic olefin copolymers (COCs) which can be used in cell phone lenses and prefilled syringes have attracted increasing attention due to their excellent and tunable thermal properties. In order to better explain the influence of COC microstructure (cyclic olefin types and content) on the glass transition mechanism, we used molecular dynamics (MD) simulations to track the evolution of free volume, diffusion coefficients, atomic mobility, trans conformation probabilities, and characteristic parameters of α-relaxation kinetics during the quenching process. MD results show that for the classic COC E-co-NB (ethylene-norbornene copolymer), an increase in cyclic olefin content from 25 to 50 mol % reduces atomic mobility, limiting the molecular chain movement at higher temperatures and improving Tg. Compared to NB, the more rigid rings in tricyclopentadiene (TCPD) and exo-1,4,4a,9,9a,10-hexahydro-9,10(1',2')-bridged phenylidene-1,4-bridged methylideneanthracene (HBM) have the following effects: (1) reducing the thermal expansion coefficient and overall chain mobility; (2) enhancing the diffusion energy barrier; (3) promoting the formation of local ordered structures; (4) accelerating α-relaxation dynamics at high temperatures and improving the dynamic fragility m. These lead to an upward shift in the temperature region where chain movement is limited and thus improve Tg and high-temperature dimensional stability. In this simulation, the correlation equation between Tg, m, and the microstructural parameters of COCs is established, which is of great significance for the development of COCs with high performance.

The mechanism of Xihuang pills' intervention in the tumour immune microenvironment for the treatment of liver cancer based on the STAT3-PDL1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pills, a time-honored Chinese compound formula with a history spanning thousands of years, have demonstrated remarkable efficacy in treating various cancers, such as breast cancer, colon cancer, and liver cancer. Clinical applications over the years have established their effectiveness. Several scholars conducting experimental studies have elucidated the potent tumor-suppressing effects of Xihuang pills. While the inhibition of tumor vascular development and prevention of tumor cell invasion and metastasis have been well-explored mechanisms, the impact on the tumor immune microenvironment has received less attention. This study focuses on investigating the immune microenvironment adjustments induced by Xihuang pills in hepatocellular carcinoma. AIM OF THE STUDY: Tumour cells will find an escape phenomenon during tumour immunotherapy, which will affect immunotherapy results. We will research the regulation of the tumour immune microenvironment, to provide a more complete and precise basis for the elucidation of the mechanism of Xihuang pills in treating cancers. It provides new research ideas for people to treat liver cancer. MATERIALS AND METHODS: Through in vivo and in vitro assessments confirming the intervention effects of Xihuang pills, we observed alterations in T cell typing, macrophage polarization, and tumor-associated cytokine levels. The primary active ingredients of Xihuang pills were identified using UPLC-MS/GC-MS, and relevant pathways in the treatment of hepatocellular carcinoma were predicted through network pharmacology. Combining the network pharmacology approach, we predicted the pathways relevant to Xihuang pills in treating hepatocellular carcinoma and experimentally validated the involvement of PD-1/PD-L1, a key immunity-related axis. RESULTS: Xihuang Pill has a regulatory effect on the tumor immune microenvironment. CONCLUSIONS: The results indicated that Xihuang pills could impact splenic lymphocyte phenotyping, macrophage polarization, and IL-6 cytokine expression in liver cancer mice. The mechanism of action was associated with the regulation of the PD-1/PD-L1 signaling pathway by the STAT3 protein.

Amplifying dual-visible-light photoswitching in aqueous media via confinement promoted triplet-triplet energy transfer.

Achieving visible-light photochromism is a long-term goal of chemists keen to exploit the opportunities of molecular photoswitches in multi-disciplinary research studies. Triplet-sensitization offers a flexible approach to building diverse visible-light photoswitches using existing photochromic scaffolds, circumventing the need for sophisticated molecular design and synthesis. Unfortunately, distance-dependence and environment-sensitivity of triplet-excited species remain as key challenges that severely impair sensitization efficiency and limit their practical availability. We present herein a nature-inspired nanoconfinement strategy in which a triplet-sensitized visible-light photoswitch/sensitizer system is assembled into nanoconfined micelles (d ∼ 40 nm). A ca. 10-fold efficiency increase of triplet-triplet energy transfer for photochromism as well as an amplified fluorescence on/off contrast upon bi-directional visible-light excitation (470/560 nm) was achieved in full aqueous media. By virtue of this, the hybrid photoswitchable system is successfully applied for both flash information encryption and multiple dynamic cell imaging assays, further proving its versatility in materials and life science.