PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide-isomerase A3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein (CRP) level and disease activity score 28 (DAS28). Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor (TCR) signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing Th1 and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

Two-Photon Photodegradation of E3 Ubiquitin Ligase Cereblon by a Ru(II) Complex: Inducing Ferroptosis in Cisplatin-Resistant Tumor Cells.

Using photodynamic therapy (PDT) to trigger nonconventional cell death pathways has provided a new scheme for highly efficient and non-side effects to drug-resistant cancer therapies. Nonetheless, the unclear targets of available photosensitizers leave the manner of PDT-induced tumor cell death relatively unpredictable. Herein, we developed a novel Ru(II)-based photosensitizer, Ru-Poma. Possessing the E3 ubiquitin ligase CRBN-targeting moiety and high singlet oxygen yield of 0.96, Ru-Poma was demonstrated to specifically photodegrade endogenous CRBN, increase lipid peroxide, downregulate GPX4 and GAPDH expression, and consequently induce ferroptosis in cisplatin-resistant cancerous cells. Furthermore, with the deep penetration of two-photon excitation, Ru-Poma achieved drug-resistant circumvention in a 3D tumor cell model. Thus, we describe the first sample of the CRBN-targeting Ru(II) complex active in PDT.

Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

Anderson critical metal phase in trivial states protected by average magnetic crystalline symmetry.

Transitions between distinct obstructed atomic insulators (OAIs) protected by crystalline symmetries, where electrons form molecular orbitals centering away from the atom positions, must go through an intermediate metallic phase. In this work, we find that the intermediate metals will become a scale-invariant critical metal phase (CMP) under certain types of quenched disorder that respect the magnetic crystalline symmetries on average. We explicitly construct models respecting average C2zT, m, and C4zT and show their scale-invariance under chemical potential disorder by the finite-size scaling method. Conventional theories, such as weak anti-localization and topological phase transition, cannot explain the underlying mechanism. A quantitative mapping between lattice and network models shows that the CMP can be understood through a semi-classical percolation problem. Ultimately, we systematically classify all the OAI transitions protected by (magnetic) groups P m , P 2 ' , P 4 ' , and P 6 ' with and without spin-orbit coupling, most of which can support CMP.

New Phenol Derivatives from the Haima Cold Seep-Derived Fungus Aspergillus subversicolor CYH-17.

Seven new phenol derivatives, subversins A-E (1-5), subversic acid A (6) and epi-wortmannine G (7); one new natural product, 4-hydroxy-7-methoxyphthalide (8); and five known compounds (9-13) were isolated from the fungus Aspergillus subversicolor CYH-17 collected from the Haima cold seep. The structures and absolute configurations of these compounds were determined via NMR, MS, optical rotation, electronic circular dichroism (ECD) calculation, X-ray diffraction analysis and comparison with the literature. Compounds 2 and 5 were two pairs of enantiomers. All compounds were tested for their α-glucosidase and acetylcholinesterase (AChE) inhibitory activity, antioxidant activity and antibacterial activity, but no obvious activity was observed among these studied compounds.

Synthesis, Structural Characterization, and Biological Activities of 1,3,4- Thiadiazole Derivatives Containing Sulfonylpiperazine Structures.

To develop novel bacterial biofilm inhibiting agents, a series of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures were designed, synthesized, and characterized using 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. Meanwhile, their biological activities were evaluated, and the ensuing structure-activity relationships were discussed. The bioassay results showed the substantial antimicrobial efficacy exhibited by most of the compounds. Among them, compound A24 demonstrated a strong efficacy with an EC50 value of 7.8 µg/mL in vitro against the Xanthomonas oryzae pv. oryzicola (Xoc) pathogen, surpassing commercial agents thiodiazole copper (31.8 µg/mL) and bismerthiazol (43.3 µg/mL). Mechanistic investigations into its anti-Xoc properties revealed that compound A24 operates by increasing the permeability of bacterial cell membranes, inhibiting biofilm formation and cell motility, and inducing morphological changes in bacterial cells. Importantly, in vivo tests showed its excellent protective and curative effects on rice bacterial leaf streak. Besides, molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are key factors between the binding of A24 and AvrRxo1-ORF1. Therefore, these results suggest the utilization of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures as a bacterial biofilm inhibiting agent, warranting further exploration in the realm of agrochemical development.

Sulfonate derivatives bearing an amide unit: design, synthesis and biological activity studies.

Pest disasters which occurs on crops is a serious problem that not only cause crop yield loss or even crop failure but can also spread a number of plant diseases.Sulfonate derivatives have been widely used in insecticide and fungicide research in recent years. On this basis, a series of sulfonate derivatives bearing an amide unit are synthesized and the biological activities are evaluated. The bioassay results showed that compounds A8, A13, A16, B1, B3, B4, B5, B10, B12 - 20, C3, C5, C9, C10, C14, C15, C17 and C19 showed 100% activity at a concentration of 500 µg/mL against the Plutella xylostella (P. xylostella). Among them, B15 which contains a thiadiazole sulfonate structure still shows 100% activity at 50 µg/mL concentration against P. xylostella and had the lowest median lethal concentration (LC50) (7.61 µg/mL) among the target compounds. Further mechanism studies are conducted on compounds with better insecticidal activity. Molecular docking results shows that B15 formed hydrophobic interactions π-π and hydrogen bonds with the indole ring of Trp532 and the carboxyl group of Asp384, respectively, with similar interaction distances or bond lengths as those of diflubenzuron. Moreover, chitinase inhibition assays are performed to further demonstrate its mode of action. In addition, the anti-bacterial activity of the series of compounds is also tested and the results showed that the series of compounds has moderate biological activity against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), with inhibition rates of 91%, 92% and 92%, 88% at the concentration of 100 µg/mL, respectively. Our study indicates that B15 can be used as a novel insecticide for crop protection.

Description of two new Megistophylla Burmeister, 1855 species from China, with a redescription of M. andrewesi Moser, 1913 (Coleoptera: Scarabaeidae: Melolonthinae).

This study presents descriptions and illustrations of two new melolonthine species: Megistophylla brevivirgata Wang & Gao, new species and M. keithi Wang & Gao, new species from Yunnan province in China. Additionally, a detailed redescription and illustration of the male of M. andrewesi Moser, 1913, and a description of its previously unknown female are provided. Finally, a key to identification of Megistophylla Burmeister, 1855 species from China is added.

Earliest Prepared core technology in Eurasia from Nihewan (China): Implications for early human abilities and dispersals in East Asia.

Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.

Near-Infrared In Vivo Imaging of Claudin-1 Expression by Orthotopically Implanted Patient-Derived Colonic Adenoma Organoids.

BACKGROUND: Claudin-1 becomes overexpressed during the transformation of normal colonic mucosa to colorectal cancer (CRC). METHODS: Patient-derived organoids expressed clinically relevant target levels and genetic heterogeneity, and were established from human adenoma and normal colons. Colonoids were implanted orthotopically in the colon of immunocompromised mice. This pre-clinical model of CRC provides an intact microenvironment and representative vasculature. Colonoid growth was monitored using white light endoscopy. A peptide specific for claudin-1 was fluorescently labeled for intravenous administration. NIR fluorescence images were collected using endoscopy and endomicroscopy. RESULTS: NIR fluorescence images collected using wide-field endoscopy showed a significantly greater target-to-background (T/B) ratio for adenoma versus normal (1.89 ± 0.35 and 1.26 ± 0.06) colonoids at 1 h post-injection. These results were confirmed by optical sections collected using endomicroscopy. Optical sections were collected in vivo with sub-cellular resolution in vertical and horizontal planes. Greater claudin-1 expression by individual epithelial cells in adenomatous versus normal crypts was visualized. A human-specific cytokeratin stain ex vivo verified the presence of human tissues implanted adjacent to normal mouse colonic mucosa. CONCLUSIONS: Increased claudin-1 expression was observed from adenoma versus normal colonoids in vivo using imaging with wide field endoscopy and endomicrosopy.

Optimizing brand loyalty through user-centric product package design: A study of user experience in dairy industry.

Objective: With the arrival of the experience economy era, changes in the marketing environment, and the evolution of consumer psychological needs, a good user experience will bring them freshness. Based on user experience, this paper analyzes the relationship among product brand image, brand trust, and brand loyalty, aiming to promote product values and improve brand loyalty and trust. Methods: Through case analysis, consumers' favorite brands were selected and conducted positioning analysis on brand color, image, package form, and so on. The study proposed a hypothetical model of user experience on brand loyalty and performed a questionnaire survey on 357 consumers. The relational model of the impact of user experience on consumers was verified using the SEM (Structural Equation Model) method. Results: It is shown that sensory experience, emotional experience, behavioral experience, and thinking experience have significant impacts on brand image; brand image apparently affects brand trust; and brand trust and image remarkably influence brand loyalty. Conclusions: Extending the concept of user experience to the fast-moving consumer goods industry will contribute to the package design of products and the theory and practice of brand loyalty. The research findings can provide effective strategies and approaches for marketers to improve product market competitiveness and enhance consumer brand stickiness.

[Effects of Microplastics on the Leaching of Nutrients and Cadmium from Soil].

The environmental effects of microplastics, which are considered a type of emerging contaminants, have attracted increasing concern due to their small size, large specific surface area, strong adsorption capacity, and low degradability. Microplastics can change soil properties and affect the migration ability of nutrients and pollutants in soil, but their effects on the leaching of soil nutrients and heavy metals have not been sufficiently studied. A soil column leaching experiment was conducted to explore the effects of polystyrene (PS) and polylactic acid (PLA) microplastics at different mass fractions (0%, 0.2%, and 2%) on the leaching of nutrients and cadmium under simulated rainfall scenarios. The results showed that increasing rainfall intensity enhanced the leaching of nutrients and cadmium from soil. During downpour conditions, 2% PS significantly increased the leaching of total nitrogen and the content of available phosphorus in soil and reduced the leaching of inorganic phosphorus and the content of ammonium nitrogen in the soil, whereas it increased the content of available potassium during heavy rain. By comparison, 2% PLA reduced the leaching of nitrate nitrogen during heavy rain and intense rainfall and decreased the content of ammonium nitrogen in soil during intense rainfall and downpour conditions and the content of total nitrogen in soil during downpours. In addition, 0.2% PLA significantly increased cadmium leaching during downpours. To conclude, the effects of microplastics on the leaching of nutrients and cadmium were dependent on the type and concentration of microplastics, as well as the rainfall level. Our findings showed that the microplastics derived from both nondegradable PS and biodegradable PLA could affect the leaching of nutrients and heavy metals from soil.

Salvianolic acid B attenuates diabetic nephropathy through alleviating ADORA2B, NALP3 in flammasome, and NFκB activity.

Diabetic nephropathy is one of the microvascular complications of diabetes. This study is aimed at investigating the role and mechanisms of salvianolic acid B (Sal B) in diabetic nephropathy. High glucose (HG)-induced human renal tubular epithelial HK-2 cells were treated with Sal B, BAY-60-6583 (agonist of adenosine 2B receptor), or PSB-603 (antagonist of adenosine 2B receptor) for 24 h. Adenosine A2b receptor (ADORA2B), NACHT, leucine-rich repeat (LRR), and pyrin (PYD) domains-containing protein 3 (NALP3), and nuclear factor Kappa B (NFκB) expressions, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels were examined. Following 6 weeks of Sal B treatment, db/db mice blood and kidney tissue were harvested for biochemical detection with hematoxylin-eosin (H&E), Masson's, periodic acid schiff (PAS), and Sirius red staining and detection of ADORA2B, NALP3, NFκB, interleukin 1ß (IL-1ß), and toll-like receptor 4 (TLR4) activity. NFκB, NALP3, and ADORA2B were found to be downregulated in Sal B treated HK-2 cells exposed to high glucose (HG), accompanied by elevated levels of MMPs and reduced intracellular ROS production. Sal B-treated diabetic mice had the improvement in body weight, water intake, hyperglycemia, hyperlipidemia, and liver and kidney function. Altogether, Sal B attenuates HG-induced kidney tubule cell injury and diabetic nephropathy in diabetic mice, providing clues to other novel mechanisms by which Sal B is beneficial in diabetic nephropathy.

8R-methoxy-9R-hydroxyl-fumitremorgin C, a new diketopiperazine alkaloid from Haima cold seep-derived fungus Aspergillus fumigatus CYH-5.

One novel diketopiperazine derivative 8R-methoxy-9R-hydroxyl-fumitremorgin C (1), together with twelve known compounds, was separated from the fungus Aspergillus fumigatus CYH-5 collected from Haima cold seep. The structures of the compounds were identified by NMR, MS, optical rotation, hydrolysis reaction and comparing with literatures. Among them, compounds 10 and 11 exhibited inhibitory effect against bacteria. Compound 11 showed inhibitory activity on α-glucosidase and compound 8 displayed acetylcholinesterase (AchE) inhibitory activity.

Relationship between body composition and pulmonary function in the general population-a cross-sectional study in Ningxia.

Studies considering the relationship between non-obesity-related body composition and lung function are few; therefore, this study aimed to explore these correlations and effects. This cross-sectional study conducted in rural Qingtongxia City and Pingluo County, Ningxia, China, included 776 participants aged 30-75 years. Body composition and lung function were measured using direct segmental multifrequency bioelectrical impedance analysis and a digital spirometer, respectively. Their correlation was assessed using partial correlation analysis, controlling for age and smoking status, and the body composition effect on lung function was analyzed using binomial logistic regression analysis. The body components total body water content, protein content, mineral content, muscle mass, fat-free mass (FFM), skeletal muscle mass, basal metabolic volume, and chest circumference (CC) positively correlated with pulmonary function (forced vital capacity and forced expiratory volume in one second) in both sexes. Neck circumference and hip circumference positively correlated with pulmonary function in women. Additionally, lung function declines more slowly in women (odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.44-0.98, p = 0.04); CC (OR = 0.92, 95% CI = 0.86-0.98, p = 0.01) increased as a protective factor for decreased lung function. Increased waist circumference (OR = 1.04, 95% CI = 1.00-1.09, p = 0.04) was a risk factor for reduced lung function. FFM contains body composition indicators positively correlating with lung function, excluding fat-related body composition. Abdominal obesity increases the risk of decreased lung function.

Clinical value of quantitative analysis of contrast-enhanced ultrasonography in the differential diagnosis of benign and malignant pelvic tumors.

Background: Cervical cancer, endometrial cancer, and ovarian cancer are among the top 10 most common cancers in women, with ovarian cancer in particular being considered a "silent killer". Therefore, early detection, diagnosis, and treatment constitute important means of care for women's health. This study investigated the clinical value of the quantitative analysis of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign and malignant pelvic tumors. Methods: CEUS was performed on 151 patients with pelvic masses. Subsequently, a qualitative diagnosis was completed using the image enhancement features and tumor parameters. A multiparametric analysis of CEUS images was performed, which included the following parameters: arrival time (AT), time to peak (TTP), peak intensity (PI), and ascent slope (AS). In addition, the qualitative diagnostic efficiency of CEUS was assessed in a multiparametric analysis, and the results were compared with pathological findings. Results: The patients in the malignant group were older (P=0.001) and had larger lesion PI values (P<0.01) than those in the benign group. The PI difference (PId) and the AS difference (ASd) showed statistical differences (P<0.01) between the myometrium and lesion tissues in the same patient. Moreover, the PId and ASd showed the largest receiver operating characteristic (ROC) curve and area under the ROC curve (AUC), with sensitivities of 90.9% and 91.7% and specificities of 86.4% and 72.5%, respectively. Conclusions: The quantitative analysis of CEUS provides a new, simpler, and more accurate method for the differential diagnosis of benign and malignant pelvic masses in clinical practice. The sensitivities and specificities of PId and ASd were higher compared to other parameters from the same patient.

Regulation of epithelial transitional states in murine and human pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease arising from impaired regeneration of the alveolar epithelium after injury. During regeneration, type 2 alveolar epithelial cells (AEC2s) assume a transitional state that upregulates multiple keratins and ultimately differentiate into AEC1s. In IPF, transitional AECs accumulate with ineffectual AEC1 differentiation. However, whether and how transitional cells cause fibrosis, whether keratins regulate transitional cell accumulation and fibrosis, and why transitional AECs and fibrosis resolve in mouse models but accumulate in IPF are unclear. Here, we show that human keratin 8 (KRT8) genetic variants were associated with IPF. Krt8-/- mice were protected from fibrosis and accumulation of the transitional state. Keratin 8 (K8) regulated the expression of macrophage chemokines and macrophage recruitment. Profibrotic macrophages and myofibroblasts promoted the accumulation of transitional AECs, establishing a K8-dependent positive feedback loop driving fibrogenesis. Finally, rare murine transitional AECs were highly senescent and basaloid and may not differentiate into AEC1s, recapitulating the aberrant basaloid state in human IPF. We conclude that transitional AECs induced and were maintained by fibrosis in a K8-dependent manner; in mice, most transitional cells and fibrosis resolved, whereas in human IPF, transitional AECs evolved into an aberrant basaloid state that persisted with progressive fibrosis.

A Soybean Sucrose Non-Fermenting Protein Kinase 1 Gene, GmSNF1, Positively Regulates Plant Response to Salt and Salt-Alkali Stress in Transgenic Plants.

Soybean is one of the most widely grown oilseed crops worldwide. Several unfavorable factors, including salt and salt-alkali stress caused by soil salinization, affect soybean yield and quality. Therefore, exploring the molecular basis of salt tolerance in plants and developing genetic resources for genetic breeding is important. Sucrose non-fermentable protein kinase 1 (SnRK1) belongs to a class of Ser/Thr protein kinases that are evolutionarily highly conserved direct homologs of yeast SNF1 and animal AMPKs and are involved in various abiotic stresses in plants. The GmPKS4 gene was experimentally shown to be involved with salinity tolerance. First, using the yeast two-hybrid technique and bimolecular fluorescence complementation (BiFC) technique, the GmSNF1 protein was shown to interact with the GmPKS4 protein. Second, the GmSNF1 gene responded positively to salt and salt-alkali stress according to qRT-PCR analysis, and the GmSNF1 protein was localized in the nucleus and cytoplasm using subcellular localization assay. The GmSNF1 gene was then heterologously expressed in yeast, and the GmSNF1 gene was tentatively identified as having salt and salt-alkali tolerance function. Finally, the salt-alkali tolerance function of the GmSNF1 gene was demonstrated by transgenic Arabidopsis thaliana, soybean hairy root complex plants overexpressing GmSNF1 and GmSNF1 gene-silenced soybean using VIGS. These results indicated that GmSNF1 might be useful in genetic engineering to improve plant salt and salt-alkali tolerance.

Pancreatic draining lymph nodes (PLNs) serve as a pathogenic hub contributing to the development of type 1 diabetes.

Type 1 diabetes (T1D) is a chronic, progressive autoinflammatory disorder resulting from the breakdown of self-tolerance and unrestrained ß cell-reactive immune response. Activation of immune cells is initiated in islet and amplified in lymphoid tissues, especially those pancreatic draining lymph nodes (PLNs). The knowledge of PLNs as the hub of aberrant immune response is continuously being replenished and renewed. Here we provide a PLN-centered view of T1D pathogenesis and emphasize that PLNs integrate signal inputs from the pancreas, gut, viral infection or peripheral circulation, undergo immune remodeling within the local microenvironment and export effector cell components into pancreas to affect T1D progression. In accordance, we suggest that T1D intervention can be implemented by three major ways: cutting off the signal inputs into PLNs (reduce inflammatory ß cell damage, enhance gut integrity and control pathogenic viral infections), modulating the immune activation status of PLNs and blocking the outputs of PLNs towards pancreatic islets. Given the dynamic and complex nature of T1D etiology, the corresponding intervention strategy is thus required to be comprehensive to ensure optimal therapeutic efficacy.

Improved bone and renal safety in younger tenofovir disoproxil fumarate experienced chronic hepatitis B patients after switching to tenofovir alafenamide or entecavir.

INTRODUCTION AND OBJECTIVES: Renal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). MATERIALS AND METHODS: This retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. RESULTS: At baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary ß2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. CONCLUSIONS: Younger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.