Identification and functional characterization of the chitinase and chitinase-like gene family in Myzus persicae (Sulzer) during molting.

BACKGROUND: The crucial role of insect chitinase in molting, pupation, and emergence renders it a promising target for pest control strategies. Despite the extensive investigation of chitinase genes in various pests, there is still a lack of systematic identification and functional analysis related to aphid chitinase. RESULTS: We systematically identified a total of nine chitinase/chitinase-like genes and one ENGase gene, which included eight Cht genes, one IDGF gene, and one ENGase gene. Through phylogenetic analysis, the chitinase proteins were classified into nine distinct groups (I, II, III, V, VI, VIII, X, other, and ENGase). The expression profile revealed that the epidermis exhibited relatively high expression levels for three chitinase genes: MpCht5, MpCht7, and MpCht10. Furthermore, transcriptional levels of nine chitinase genes were up-regulated following treatment with 20-hydroxyecdysone (20E) hormone. Silencing MpCht3, MpCht5, MpCht7, MpCht10, and MpCht11-2 via RNA interference (RNAi) during the molting stage resulted in nymph shrinking, hindering normal molting and leading to death. Additionally, it was observed that silencing of MpIDGF induced the body color of the aphids to change from reddish brown to colorless after molting, culminating in eventual mortality. CONCLUSION: Our findings suggest that chitinase/chitinase-like genes play a crucial role in the molting process of Myzus persicae. Utilizing RNAi technology, we aimed to elucidate the precise function of MpCht genes in the molting mechanism of M. persicae, this discovery establishes a significant theoretical foundation for future research on aphid control, with chitinase as the target. © 2024 Society of Chemical Industry.

Draft genome sequence data of Pythium cedri Chen 4, the causal pathogen of deodar cedar root rot.

Pythium species are distributed globally, with certain members playing significant roles as plant and animal pathogens. Pythium cedri Chen 4 has been identified as a pathogenic isolate responsible for causing root rot on Cedrus deodara. Here, a comprehensive genome-wide sequence of P. cedri strain Chen 4 utilizing the Illumina NovaSeq sequencing platform and a Pacific Biosciences Sequel sequencing platform is presented. The genome of P. cedri strain Chen 4 was assembled into 150 contigs containing a combined size of 41.25 Mb, N50 value of 1,717,859 bp and N90 value of 431,829 bp. Genome annotation revealed 14,077 protein-encoding genes and 364 of the 1016 predicted proteins were putative effectors. The present work enriches the genetic resources of P. cedri for studying its evolution and can contribute to a better understanding of P. cedri-host interaction.

N-Acetylcysteine Inhibits Coxsackievirus B3 Replication by Downregulating Eukaryotic Translation Elongation Factor 1 Alpha 1.

Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1.

The pro-atherogenic effects and the underlying mechanisms of chronic bisphenol S (BPS) exposure in apolipoprotein E-deficient mice.

Atherosclerosis (AS) and its related cardiovascular diseases (CVDs) remain the most frequent cause of morbidity and mortality worldwide. Researches showed that bisphenol A (BPA) exposure might exacerbate AS progression. However, as an analogue of BPA, little is known about the cardiovascular toxicity of bisphenol S (BPS), especially whether BPS exposure has the pro-atherogenic effects in mammals is still unknown. Here, we firstly constructed an apolipoprotein E knockout (ApoE-/-) mouse model and cultured cells to investigate the risk of BPS on AS and explore the underlying mechanisms. Results showed that prolonged exposure to 50 µg/kg body weight (bw)/day BPS indeed aggravated AS lesions both in the en face aortas and aortic sinuses of ApoE-/- mice. Moreover, BPS were found to be implicated in the AS pathological process: 1) stimulates adhesion molecule expression to promote monocyte-endothelial cells (ECs) adhesion with 3.6 times more than the control group in vivo; 2) increases the distribution of vascular smooth muscle cells (VSMCs) with 9.3 times more than the control group in vivo, possibly through the migration of VSMCs; and 3) induces an inflammatory response by increasing the number of macrophages (MACs), with 3.7 times more than the control group in vivo, and the release of inflammatory mediators. Furthermore, we have identified eight significant AS-related genes induced by BPS, including angiopoietin-like protein 7 (Angptl17) and lipocalin-2 (Lcn2) in ECs; matrix metalloproteinase 9 (Mmp13), secreted phosphoprotein 1 (Spp1), and collagen type II alpha 1 (Col2a1) in VSMCs; and kininogen 1 (Kng1), integrin alpha X (Itgax), and MAC-expressed gene 1 (Mpeg1) in MACs. Overall, this study firstly found BPS exposure could exacerbate mammalian AS and might also provide a theoretical basis for elucidating BPS and its analogues induced AS and related CVDs.

Application of Chairside CAD/CAM and Its Influencing Factors among Chinese Dental Practitioners: a Crosssectional Study.

OBJECTIVE: To examine the increased use of chairside CAD/CAM among Chinese dental practitioners, and to explore the existing barriers influencing its further application and satisfaction levels. METHODS: A semi-structured questionnaire was developed to gather respondents' demographic information, as well as their experiences and behaviours regarding the implementation of chairside CAD/CAM. A specialised web-based survey system and WeChat were used to display and distribute the final questionnaire. Then, the data were analysed with Chi-square tests and regression analyses to determine the effects of various demographic variables on chairside CAD/ CAM applications. RESULTS: A total of 1,969 questionnaire responses were included in the analyses. Chairside CAD/ CAM systems were used by 36.9% of participants, with a higher usage rate observed among prosthodontists (60.0%) and dental practitioners holding a PhD degree (57.7%). Chairside CAD/ CAM-fabricated prostheses were most commonly used in the posterior maxilla (83.3%) and mandible (86.0%), followed by the anterior maxilla and mandible (63.8% and 48.6%, respectively). Major barriers to further application included high initial investment, frequent updates of equipment and software programs, and a lack of expertise in chairside CAD/CAM usage. CONCLUSION: Most dental practitioners did not use chairside CAD/CAM systems. The application rate was significantly influenced by sex, location, educational background, department and type of healthcare facility. Chairside CAD/CAM users showed limited satisfaction with the aesthetic performance of the fabricated prostheses. To improve the popularity of chairside CAD/CAM systems, especially among dental practitioners lacking advanced academic degrees, it is highly advisable to optimise CAD software programs and offer comprehensive training opportunities.

Neoadjuvant radiation target volume definition in esophageal squamous cell cancer: a multicenter recommendations from Chinese experts.

BACKGROUND: This study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China. METHODS: From February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1-6 and the second for cases 7-9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test. RESULTS: The second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76-0.81; mean Hmean = 2.11-3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63-0.64; mean Hmean = 5.66-7.34 cm; DSC and Hmean: P < 0.050 between rounds), leading to the formation of a consensus and an atlas for ESCC nRT target volume delineation. A proposal was reached through evaluating target volume delineations, analyzing questionnaire survey outcomes, and reviewing pertinent literature. CONCLUSIONS: We have developed guidelines and an atlas for target volume delineation in nRT therapy for ESCC in China. These resources are designed to facilitate more consistent delineation of target volumes in both clinical practice and clinical trials.

Impaired TGF-ß signaling via AHNAK family mutations elicits an esophageal cancer subtype with sensitivities to genotoxic therapy and immunotherapy.

BACKGROUND: Genome instability (GI) is a hallmark of esophageal squamous cell carcinoma (ESCC) while factors affecting GI remain unclear. METHODS: Here, we aimed to characterize genomic events representing specific mechanisms of GI based on 201 ESCC samples and validated our findings at the patient, single-cell and cancer cell-line levels, including a newly generated multi-omics dataset of the trial NCT04006041. RESULTS: A two-gene (AHNAK and AHNAK2) mutation signature was identified to define the "AHNAK1/2-mutant" cancer subtype. Single-cell-assisted multi-omics analysis showed that this subtype had a higher neoantigen load, active antigen presentation, and proficient CD8 + T cell infiltrations, which were validated at pan-cancer levels. Mechanistically, AHNAK1/2-mutant ESCC was characterized by impaired response of TGF-ß and the inefficient alternative end-join repair (Alt-EJ) that might promote GI. Knockdown of AHNAK in ESCC cell lines resulted in more Alt-EJ events and increased sensitivities to cisplatin. Furthermore, this two-gene signature accurately predicted better responses to DNA-damaging therapy in various clinical settings (HR ≈ 0.25). The two-gene signature predicted higher pCR rates in ESCCs receiving neoadjuvant immunotherapy-involved treatment. Finally, a molecular classification scheme was built and outperformed established molecular typing models in the prognosis stratification of ESCC patients. CONCLUSION: Our study extended our understanding of the AHNAK family in promoting GI and selecting treatment responders of ESCC.

Photoexcited Cryptochrome 1 Interacts With SPCHLESS to Regulate Stomatal Development in Arabidopsis.

Stomata are epidermal openings that facilitate plant-atmosphere gas and water exchange during photosynthesis, respiration and water evaporation. SPEECHLESS (SPCH) is a master basic helix-loop-helix (bHLH) transcription factor that determines the initiation of stomatal development. It is known that blue light promotes stomatal development through the blue light photoreceptor cryptochromes (CRYs, CRY1 and CRY2). Whether CRYs regulate stomatal development through directly modulating SPCH is unknown. Here, we demonstrate by biochemical studies that CRY1 physically interacts with SPCH in a blue light-dependent manner. Genetic studies show that SPCH acts downstream of CRY1 to promote stomatal development in blue light. Furthermore, we show that CRY1 enhances the DNA-binding activity of SPCH and promotes the expression of its target genes in blue light. These results suggest that the mechanism by which CRY1 promotes stomatal development involves positive regulation of the DNA-binding activity of SPCH, which is likely mediated by blue light-induced CRY1-SPCH interaction. The precise regulation of SPCH DNA-binding activity by CRY1 may allow plants to optimize stomatal density and pattern according to ambient light conditions.

Phylogeography and Population Variation in Prunus discoidea (Prunus subg. Cerasus) in China.

Prunus discoidea is a unique cherry blossom germplasm resource native to China. It is widely distributed across the provinces of Anhui, Zhejiang, Jiangxi, Jiangsu, and Henan, with significant variation. We employed phylogeographic analysis to reveal the evolutionary history of P. discoidea to better understand its genetic diversity and structure. This study provides more accurate molecular insights for the effective conservation and utilization of this germplasm resource. We conducted a phylogeographic analysis of 348 individual plants from 13 natural populations using three fragments (rpoB, rps16, and trnD-E) of chloroplast DNA (cpDNA) and one fragment (ITS) of ribosomal DNA. The results revealed that P. discoidea demonstrates a significant level of genetic diversity (Hd = 0.782; Rd = 0.478). Gene flow among populations was limited, and the variation within populations was the main source of genetic diversity in P. discoidea (among populations: 34.26%, within populations: 65.74%). Regarding genetic differences among populations, Nst (0.401) showed greater differences than Gst (0.308; p < 0.05), demonstrating that there was a significant geographical structure of lineage. One lineage was the central region of Anhui and the western region of Hubei. The other lineage was the Jiangsu region and the Zhejiang region. P. discoidea diverged from Prunus campanulata approximately 1.5 million years ago, during the Pleistocene epoch. This study provides a scientific theoretical basis for the conservation and utilization of germplasm resources of P. discoidea.

Research Progress on the Microstructure Evolution Mechanisms of Al-Mg Alloys by Severe Plastic Deformation.

Al-Mg alloys are widely used as important engineering structural materials in aerospace engineering, transportation systems, and structural constructions due to their low density, high specific strength, corrosion resistance, welding capability, fatigue strength, and cost-effectiveness. However, the conventional Al-Mg alloys can no longer fully satisfy the demands of practical production due to difficulties caused by many defects. The high strength of Al-Mg alloys as non-heat treatment precipitation-strengthened alloys is achieved primarily by solid solution strengthening along with work hardening rather than precipitation strengthening. Therefore, severe plastic deformation (SPD) techniques can be often used to produce ultrafine-grained structures to fabricate ultra-high strength aluminum alloys. However, this approach often achieves the strengthening of material at the cost of reduced ductility. This paper comprehensively summarizes the various approaches of ultrafine/nanocrystalline materials for enhancing their plasticity, elaborates on the creation of a bimodal microstructure within the alloy, and discusses the formation of a nanotwin microstructure within the alloy and the incorporation of dispersed nanoparticles. The mechanisms underlying both the strengthening and toughening during large plastic deformation in aluminum alloys are summarized, and the future research direction of high-performance ultrafine crystalline and nanocrystalline Al-Mg aluminum alloys is prospected.

The Development and Application of Tritium-Labeled Compounds in Biomedical Research.

With low background radiation, tritiate compounds exclusively emit intense beta particles without structural changes. This makes them a useful tool in the drug discovery arsenal. Thanks to the recent rapid progress in tritium chemistry, the preparation and analysis of tritium-labeled compounds are now much easier, simpler, and cheaper. Pharmacokinetics, autoradiography, and protein binding studies have been much more efficient with the employment of tritium-labeled compounds. This review provides a comprehensive overview of tritium-labeled compounds regarding their properties, synthesis strategies, and applications.

Polysialic acid driving cardiovascular targeting co-delivery 1,8-cineole and miR-126 to synergistically alleviate lipopolysaccharide-induced acute cardiovascular injury.

Infection-induced cardiovascular damage is the primary pathological mechanism underlying septic cardiac dysfunction. This condition affects the majority of patients in intensive care unit and has an unfavorable prognosis due to the lack of effective therapies available. Vascular cell adhesion molecule-1 (VCAM-1) plays a vital role in coordinating the inflammatory response and recruitment of leukocytes in cardiac tissue, making it a potential target for developing novel therapies. MicroRNA-126 (miR-126) has been shown to downregulate VCAM-1 expression in endothelial cells, reducing leukocyte adhesion and exerting anti-inflammatory effects. Therefore, this work described a polysialic acid (PSA) modified ROS-responsive nanosystem to targeted co-delivery 1,8-Cineole and miR-126 for mitigating septic cardiac dysfunction. The nanosystem consists of 1,8-Cineole nanoemulsion (CNE) conjugated with PEI/miR126 complex by a ROS-sensitive linker, with PSA on its surface to facilitate targeted delivery via specific interactions with selectins on endothelial cells. CNE has demonstrated protective effects against inflammation in the cardiovascular system and synergistic anti-inflammatory effects when combined with miR-126. The targeted nanosystem successfully delivered miR-126 and 1,8-Cineole to the injured heart tissues and vessels, reducing inflammatory responses and improving cardiac function. In summary, this work provides a promising therapy for alleviating the inflammatory response in sepsis while boosting cardiovascular protection.

Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.

Mitochondrial-nuclear communication plays a vital role in maintaining cellular homeostasis. MOTS-c, a short peptide derived from the 12S rRNA of mitochondrial DNA, has been suggested as a retrograde mitochondrial signal. Although recent clinical studies have suggested a possible link between MOTS-c and human cancer, the role of MOTS-c in tumorigenesis has yet to be investigated. Here, MOTS-c levels are found to be reduced in both serum and tumor tissues from ovarian cancer (OC) patients, which are associated with poor patients' prognosis. Exogenous MOTS-c inhibits the proliferation, migration and invasion of OC cells, and induces cell cycle arrest and apoptosis. Mechanistically, MOTS-c interacts with LARS1 and promotes its ubiquitination and proteasomal degradation. In addition, USP7 was identified as a deubiquitinase of LARS1, and MOTS-c can attenuates USP7-mediated LARS1 deubiquitination by competing with USP7 for binding to LARS1. Besides, LARS1 was found to be increased and play an important oncogenic function in OC. More importantly, MOTS-c displays a marked anti-tumor effect on OC growth without systemic toxicity in vivo. In conclusion, this study reveals a crucial role of MOTS-c in OC and provides a possibility for MOTS-c as a therapeutic target for the treatment of this manlignacy.

Targeted V-type peptide-decorated nanoparticles prevent colitis by inhibiting endosomal TLR signaling and modulating intestinal macrophage polarization.

Inflammatory bowel disease (IBD) has become a serious and challenging health problem globally without curative medical treatments. Mounting evidence suggests that intestinal macrophages and their phenotypes are key players in the pathogenesis of IBD. Modulating the phenotypes and functions of intestinal macrophages through targeted interventions could be a promising approach to manage detrimental gut inflammation in IBD. In this study, we rationally design and fabricate a novel class of V-type peptide-decorated nanoparticles, VP-NP, with potent anti-inflammatory activity. Such a design allows two functional motifs FFD in a single peptide molecule to enhance the bioactivity of the nanoparticles. As expected, VP-NP exhibits a strong inhibitory activity on endosomal Toll-like receptor (TLR) signaling. Surprisingly, VP-NP can inhibit M1 polarization while facilitating M2 polarization in mouse bone marrow-derived macrophages through regulating the key transcription factors NF-κB, STAT1 and PPAR-γ. Mechanistically, VP-NP is internalized by macrophages in the endosomes, where it blocks endosomal acidification to inhibit endosomal TLR signaling; the transcriptomic analysis reveals that VP-NP potently down-regulates many genes in TLR, NF-κB, JAK-STAT, and cytokine/chemokine signaling pathways associated with inflammatory responses. In a colitis mouse model, the intraperitoneally administered VP-NP effectively alleviates the disease activities by decreasing colon inflammation and injuries, pro-inflammatory cytokine production, and myeloid cell infiltration in the gut. Furthermore, VP-NP primarily targets intestinal macrophages and alters their phenotypes from inflammatory M1-type toward the anti-inflammatory M2-type. This study provides a new nanotherapeutic strategy to specifically regulate macrophage activation and phenotypes through a dual mechanism to control gut inflammation, which may augment current clinical treatments for IBD.

A Meta-Analysis and Meta-Regression of the Efficacy, Toxicity, and Quality of Life Outcomes Following Prostate-Specific Membrane Antigen Radioligand Therapy Utilising Lutetium-177 and Actinium-225 in Metastatic Prostate Cancer.

BACKGROUND AND OBJECTIVE: Management of metastatic prostate cancer (mPCa) presents significant challenges. In this systematic review, meta-analysis, and meta-regression, the efficacy, safety, and quality of life (QoL) outcomes of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) utilising lutetium-177 ([177Lu]Lu-PSMA) and actinium-225 ([225Ac]Ac-PSMA) were assessed. METHODS: A detailed literature search across PubMed/Medline, EMBASE, Web of Science, Scopus, and Cochrane Library was conducted, culminating in the inclusion of 100 studies involving 8711 patients. Data on prostate-specific antigen (PSA) responses, toxicity profiles, and QoL and survival outcomes were analysed. Proportional meta-analyses and meta-regression analyses were performed. KEY FINDINGS AND LIMITATIONS: The estimated proportion of patients with PSA decline ≥50% was 0.49 for [177Lu]Lu-PSMA and 0.60 for [225Ac]Ac-PSMA in mPCa, particularly metastatic castration-resistant prostate cancer. A meta-regression analysis indicated an association between the cumulative amount of administered activity and the proportion of PSA ≥50% decline. Positive PSA responses were observed alongside improved overall survival across both therapies. Our analyses also identified the key factors associated with PSA responses and survival outcomes, including baseline haemoglobin level, and the presence of visceral metastases. Although anaemia was commonly observed, with [177Lu]Lu-PSMA, severe toxicities were infrequent. Improved QoL was observed following [177Lu]Lu-PSMA therapy, whereas it remained stable following the second cycle of [225Ac]Ac-PSMA treatment. Heterogeneity across studies for PSA responses and toxicity profiles is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our findings suggest an association between PRLT and reductions in PSA levels, as well as associations with enhanced survival outcomes in mPCa. Furthermore, our analysis shows a low incidence of severe toxicity associated with this treatment. These observations highlight the important role of PRLT in the management of mPCa.

Does surgeon-performed intraoperative wire localization allow for lower margin positivity rates compared to radiologist-performed preoperative localization in early breast cancer?

BACKGROUND: This study compares positive margin rates in breast conserving surgery (BCS) for early breast cancer using two localization techniques: surgeon-performed intraoperative ultrasound-guided wire localization (IOWL) versus radiologist-performed preoperative wire localization (POWL). METHODS: Patients with unifocal breast cancer undergoing BCS with follow-up at a single institution were retrospectively identified. Factors associated with positive margins were identified. RESULTS: 177 patients underwent IOWL (N â€‹= â€‹85) or POWL (N â€‹= â€‹92). There was a significantly lower rate of positive margins for IOWL vs. POWL (7.1 â€‹% vs. 23.9 â€‹%, p â€‹= â€‹0.002) and a corresponding lower rate of re-excision for IOWL vs. POWL (5.9 â€‹% vs. 18.5 â€‹%, p â€‹= â€‹0.011). Presence of DCIS was associated with positive margins (p â€‹= â€‹0.015). After adjusting for presence of DCIS, tumor size, and volume of tissue removed, the positive margin rate was significantly lower in the IOWL group compared to the POWL group (aOR 0.34, 95 â€‹% CI 0.13-0.93). CONCLUSIONS: In this study, adjusted analysis favored IOWL in achieving negative tumor margins. Prospective studies are needed to further explore the impact of IOWL on quality, cost-effectiveness, and patient experience.

[Analysis of Spatial Distribution of Ecosystem Services and Driving Factors in Northeast China].

Northeast China is an important ecological barrier in China, and an in-depth understanding of the spatial distribution in ecosystem services （ESs）, and the driving factors is crucial for realizing the subsequent management and protection of ESs. In the study, we quantitatively assessed the characteristics of spatial distribution in ESs in Northeastern China using the InVEST, RWEQ, and RUSLE models and identified the driving factors of ESs spatial distribution in conjunction with the geodetector based on meteorological data, remote sensing data, and socio-economic data. The results showed that the spatial distribution of ESs in Northeast China had obvious spatial heterogeneity. The high values of habitat quality （HQ）, carbon sequestration （CS） services, and soil conservation （SC） services were mainly distributed in the northern part of the four eastern leagues of the Inner Mongolia Autonomous Region, the northern part of Heilongjiang Province, and the eastern part of Northeast China, which were high in fraction vegetation cover, and low values were mainly found in southwestern and eastern Heilongjiang Province, western Jilin Province, and western Liaoning Province. The high values of the water yield （WY） service and wind prevention and sand fixation （WPSF） service were distributed in the east of the Inner Mongolia Autonomous Region and the east of Liaoning Province. The high values of WY services and WPSF services were distributed in the eastern part of Northeast China and the four eastern provinces of the Inner Mongolia Autonomous Region. According to the geodetector results, slope had the strongest explanatory power for the spatial distribution of SC services with a q-value of 0.31, land use/cover change had the strongest explanatory power for the spatial distribution of HQ and CS services with q-values of 0.64 and 0.52, respectively, and fraction vegetation coverage and annual precipitation had the strongest explanatory power for the spatial distribution of WPSF and WY services with q-values of 0.24 and 0.64, respectively, and there were interactions among all the driving factors. The spatial distribution of ESs in Northeast China was mainly influenced by natural factors. The results will provide a scientific basis for subsequent management and enhancement of ESs in Northeast China.

Effect of tibia-first, restricted functional alignment technique on gap width changes, and component positioning in robotic arm-assisted total knee arthroplasty.

PURPOSE: This study aims to quantitatively assess the predictability of post-resection gap dimensions and the attainment of balanced gaps using robotic arm-assisted total knee arthroplasty (TKA). METHODS: This retrospective cohort study included 100 consecutive patients who underwent robotic arm-assisted TKA for knee osteoarthritis using a restricted functional alignment (FA) technique. Tibial cuts were performed based on preoperative tibial anatomy within predefined boundaries, followed by femoral component adjustments according to tensioned soft tissues to optimise gap balance. The primary outcome was the proportion of balanced gaps, defined as differential laxities of ≤2 mm, across extension, flexion, lateral, and medial gap measurements. Ligament balancing in lateral and medial compartments was assessed using a robotic system at 10° and 90° flexion to evaluate if restricted FA facilitated a balanced knee. Secondary outcomes included implant alignment, resection depth, and patient-reported outcome measures (PROMs). RESULTS: Significant increases in both lateral and medial gaps at 10° and 90° flexion were observed following tibial and femoral bone resections (p < 0.001). At extension, average gap changes were 0.9 mm (lateral) and 1.6 mm (medial) after tibial cuts, and 0.5 mm (lateral) and 1.2 mm (medial) after femoral cuts. At 90° flexion, changes were 0.3 mm (lateral) and 1.7 mm (medial) following tibial cuts, and 1.0 mm (lateral) and 1.4 mm (medial) after femoral cuts. Despite these variations, the tibia-first, gap-balancing technique achieved overall balance in 98% of gap measurements. The tibial component was placed at an average of 2.1° varus, while the femoral component was positioned at 0.3° varus and 1.3° external rotation relative to the surgical transepicondylar axis. Significant improvements in PROMs were noted between preoperative and one-year postoperative evaluations (all p < 0.05). CONCLUSIONS: The tibia-first, restricted FA technique achieved a well-balanced knee in 98% of cases, despite inconsistent gap increments observed between initial assessments and post-resection. LEVEL OF EVIDENCE: Therapeutic Level IV.

Discovery of a Highly Potent and Selective Inhibitor Targeting Protein Lysine Methyltransferase NSD2.

The histone lysine methyltransferase NSD2 has been recognized as an attractive target for cancer treatment, due to the functional implication of its dysregulation in the initiation and progression of many cancers. Although considerable efforts have been made to develop NSD2 small-molecule inhibitors, highly potent and selective ones are still rarely available till now. Here, we report the discovery of a series of novel NSD2 inhibitors via an extensive SAR exploration of the privileged quinazoline scaffold within compound 8. The most promising compound 42 showed excellent NSD2 enzymatic inhibitory activity and good antiproliferative activity in cells. In addition, it demonstrated favorable pharmacokinetic properties and significantly inhibited the tumor growth in a RS411 tumor xenograft model with good safety. Taken together, compound 42 could be a promising NSD2 inhibitor and deserves further investigation.

[Trend analysis and regulatory strategies for traditional Chinese medicine formula granules].

With the advent of the "post-pilot era" of traditional Chinese medicine formula granules, there are still a series of policy, technical, and industrial issues that need to be addressed in their production, regulation, and application practices. This article systematically reviews the development history and relevant policy evolution of traditional Chinese medicine formula granules, and summarizes the current industrial status in terms of quality standards, medical insurance payments, and market landscape. Based on a comparative analysis and positioning discussion between traditional Chinese medicine formula granules and traditional herbal decoctions, it is believed that the following practical issues still exist in this field:(1)A reasonable competitive evolution mechanism has not yet been formed, making it difficult to "improve quality and efficiency" of products;(2)The number of national standards is limited, and local standards operate independently;(3)Production processes are relatively constrained;(4)There is a contradiction between fixed equivalents and fluctuations in raw materials;(5)Market positioning needs to be clarified, and medication scenarios are limited. Furthermore, based on the perspective of shaping a healthy ecosystem for the traditional Chinese medicine industry and promoting rational clinical use of traditional Chinese medicine, the following suggestions are put forward:(1)Guide the formation of a product-based competitive landscape for traditional Chinese medicine formula granules;(2)Promote the establishment of a comprehensive regulatory system for the entire production process of traditional Chinese medicine formula granules;(3)Conduct systematic research on the relationship between the equivalents and intake of formula granules;(4)Break through existing application scenarios and reasonably expand the application forms of formula granules.