Mechanistic Insights into Dibasic Iminosugars as pH-Selective Pharmacological Chaperones to Stabilize Human α-Galactosidase.

The use of pharmacological chaperones (PCs) to stabilize specific enzymes and impart a therapeutic benefit is an emerging strategy in drug discovery. However, designing molecules that can bind optimally to their targets at physiological pH remains a major challenge. Our previous study found that dibasic polyhydroxylated pyrrolidine 5 exhibited superior pH-selective inhibitory activity and chaperoning activity for human α-galactosidase A (α-Gal A) compared with its monobasic parent molecule, 4. To further investigate the role of different C-2 moieties on the pH-selectivity and protecting effects of these compounds, we designed and synthesized a library of monobasic and dibasic iminosugars, screened them for α-Gal A-stabilizing activity using thermal shift and heat-induced denaturation assays, and characterized the mechanistic basis for this stabilization using X-ray crystallography and binding assays. We noted that the dibasic iminosugars 5 and 20 protect α-Gal A from denaturation and inactivation at lower concentrations than monobasic or other N-substituted derivatives; a finding attributed to the nitrogen on the C-2 methylene of 5 and 20, which forms the bifurcated salt bridges (BSBs) with two carboxyl residues, E203 and D231. Additionally, the formation of BSBs at pH 7.0 and the electrostatic repulsion between the vicinal ammonium cations of dibasic iminosugars at pH 4.5 are responsible for their pH-selective binding to α-Gal A. Moreover, compounds 5 and 20 demonstrated promising results in improving enzyme replacement therapy and exhibited significant chaperoning effects in Fabry cells. These findings suggest amino-iminosugars 5 and 20 as useful models to demonstrate how an additional exocyclic amino group can improve their pH-selectivity and protecting effects, providing new insights for the design of pH-selective PCs.

NeRF-Texture: Synthesizing Neural Radiance Field Textures.

Texture synthesis is a fundamental problem in computer graphics that would benefit various applications. Existing methods are effective in handling 2D image textures. In contrast, many real-world textures contain meso-structure in the 3D geometry space, such as grass, leaves, and fabrics, which cannot be effectively modeled using only 2D image textures. We propose a novel texture synthesis method with Neural Radiance Fields (NeRF) to capture and synthesize textures from given multi-view images. In the proposed NeRF texture representation, a scene with fine geometric details is disentangled into the meso-structure textures and the underlying base shape. This allows textures with meso-structure to be effectively learned as latent features situated on the base shape, which are fed into a NeRF decoder trained simultaneously to represent the rich view-dependent appearance. Using this implicit representation, we can synthesize NeRF-based textures through patch matching of latent features. However, inconsistencies between the metrics of the reconstructed content space and the latent feature space may compromise the synthesis quality. To enhance matching performance, we further regularize the distribution of latent features by incorporating a clustering constraint. In addition to generating NeRF textures over a planar domain, our method can also synthesize NeRF textures over curved surfaces, which are practically useful. Experimental results and evaluations demonstrate the effectiveness of our approach.

Data-Driven Distributed Predictive Control for Voltage Regulation and Current Sharing in DC Microgrids With Communication Constraints.

The use of nonideal communication networks makes communication constraints become a topical issue in the research of dc microgrids. How to design a distributed secondary control scheme for voltage recovery and accurate current sharing in islanded dc microgrids subject to communication constraints is of interest in this article. In order to restore the bus voltage to the rated value, a nonlinear element is first introduced into the primary control layer. Then, the closed-loop system of primary control is modeled as a data-driven time-varying linear system. Based on the established model, considering communication constraints, a distributed secondary predictive control strategy is developed to achieve accurate current sharing. While actively compensating for network delays and packet losses, the proposed method renders mathematical physical models unnecessary for the traditional predictive control, and simultaneously completes the multitask in dc microgrids. Finally, several case studies are conducted on a hardware microgrid experimental platform, which not only verifies the effectiveness of the designed data-driven predictive control strategy but also tests microgrid properties such as the plug-and-play ability.

Impact of nutritional support routes on mortality in acute pancreatitis: A network meta-analysis of randomized controlled trials.

BACKGROUND: Nutritional administration in acute pancreatitis (AP) management has sparked widespread discussion, yet contradictory mortality results across meta-analyses necessitate clarification. The optimal nutritional route in AP remains uncertain. Therefore, this study aimed to compare mortality among nutritional administration routes in patients with AP using consistency model. METHODS: This study searched four major databases for relevant randomized controlled trials (RCTs). Two authors independently extracted and checked data and quality. Network meta-analysis was conducted for estimating risk ratios (RRs) with 95% confidence interval (CI) based on random-effects model. Subgroup analyses accounted for AP severity and nutrition support initiation. RESULTS: A meticulous search yielded 1185 references, with 30 records meeting inclusion criteria from 27 RCTs (n = 1594). Pooled analyses showed the mortality risk reduction associated with nasogastric (NG) (RR = 0.34; 95%CI: 0.16-0.73) and nasojejunal (NJ) feeding (RR = 0.46; 95%CI: 0.25-0.84) in comparison to nil per os. Similarly, NG (RR = 0.45; 95%CI: 0.24-0.83) and NJ (RR = 0.60; 95%CI: 0.40-0.90) feeding also showed lower mortality risk than total parenteral nutrition. Subgroup analyses, stratified by severity, supported these findings. Notably, the timing of nutritional support initiation emerged as a significant factor, with NJ feeding demonstrating notable mortality reduction within 24 and 48 h, particularly in severe cases. CONCLUSION: For severe AP, both NG and NJ feeding appear optimal, with variations in initiation timings. NG feeding does not appear to merit recommendation within the initial 24 h, whereas NJ feeding is advisable within the corresponding timeframe following admission. These findings offer valuable insights for optimizing nutritional interventions in AP.

The association and underlying mechanism of the digit ratio (2D:4D) in hypospadias.

ABSTRACT: The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children's Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias (P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [DNAH8]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a (Wnt5a), Wnt5b, Smad family member 2 (Smad2), and Smad3; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase (AMPK) and nuclear respiratory factor 1 (Nrf-1); and vascular development-related genes such as myosin light chain (MLC), notch receptor 3 (Notch3), and sphingosine kinase 1 (Sphk1), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

Estimation of the tumor size at cure threshold among adult patients with adrenocortical carcinoma: A populational-based study.

Background: The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the influence of tumor size on prognostic value in adult ACC patients. Methods: The Surveillance, Epidemiology and End Results Program (SEER) was employed to identify adult ACC patients who had been diagnosed from 2004 to 2015. The "X-Tile" program determined the optimal cutoff value of tumor size. Cancer-specific survival (CSS) and overall survive (OS) were estimated. The survival outcomes and risk factors were analyzed by the Kaplan-Meier methods and the multivariable cox regression respectively. Results: A total 426 adult ACC patients were included. Univariable and multivariable cox analysis revealed age, larger tumor size and metastasis as consistent predictors of lower CSS and OS. The optimal cutoff value of tumor size was identified as 8.5 cm using X-tile software, and Kaplan-Meier method showed dramatic prognostic difference between patients with larger tumors (＞8.5 cm) and smaller tumors (≤8.5 cm) (log-rank test, P < 0.001). Subgroup analyses revealed no statistical significance and a consistent proportionate effect of tumor size on CSS and OS across all eight pre-specified subgroups. Interestingly, an additional subgroup analysis showed that ACC patients could not benefit from chemotherapy in terms of CSS and OS. Conclusion: The study suggests that tumor size is a crucial prognostic factor in ACC patients and a cutoff value 8.5 cm might indicate a poor outcome. Given the limitations of the available data, it is challenging to conclusively determine the benefit of chemotherapy in adult ACC patients across different tumor size ranges.

Yield-related quantitative trait loci identification and lint percentage hereditary dissection under salt stress in upland cotton.

Salinity is frequently mentioned as a major constraint in worldwide agricultural production. Lint percentage (LP) is a crucial yield-component in cotton lint production. While the genetic factors affect cotton yield in saline soils are still unclear. Here, we employed a recombinant inbred line population in upland cotton (Gossypium hirsutum L.) and investigated the effects of salt stress on five yield and yield component traits, including seed cotton yield per plant, lint yield per plant, boll number per plant, boll weight, and LP. Between three datasets of salt stress (E1), normal growth (E2), and the difference values dataset of salt stress and normal conditions (D-value), 87, 82, and 55 quantitative trait loci (QTL) were detectable, respectively. In total, five QTL (qLY-Chr6-2, qBNP-Chr4-1, qBNP-Chr12-1, qBNP-Chr15-5, qLP-Chr19-2) detected in both in E1 and D-value were salt related QTL, and three stable QTL (qLP-Chr5-3, qLP-Chr13-1, qBW-Chr5-5) were detected both in E1 and E2 across 3 years. Silencing of nine genes within a stable QTL (qLP-Chr5-3) highly expressed in fiber developmental stages increased LP and decreased fiber length (FL), indicating that multiple minor-effect genes clustered on Chromosome 5 regulate LP and FL. Additionally, the difference in LP caused by Gh_A05G3226 is mainly in transcription level rather than in the sequence difference. Moreover, silencing of salt related gene (GhDAAT) within qBNP-Chr4-1 decreased salt tolerance in cotton. Our findings shed light on the regulatory mechanisms underlining cotton salt tolerance and fiber initiation.

Dicyanoisophorone-based near-infrared fluorescent probe with large Stokes shift for the monitoring and bioimaging of hypochlorite.

Hypochlorite (ClO-), as one of reactive oxygen species (ROS), is closely linked to various illnesses and is essential for the proper functioning of immune system. Hence, monitoring and assessing ClO- levels in organisms are extremely important for the clinical diagnosis of ClO--related disorders. In this study, a novel ClO--selective fluorescent probe, DCP-ClO, was synthesized with dicyanoisophorone-xanthene unit as parent fluorophore, which displayed excellent selectivity towards ClO-, near-infrared emission (755 nm), large Stokes shift (100 nm), real-time response to ClO-, high sensitivity (LOD = 3.95 × 10-8 M), and low cytotoxicity. The recognition mechanism of DCP-ClO towards ClO- was confirmed to be a typical ICT process by HPLC-MS, HR-MS, 1H NMR and theoretical calculations. Meanwhile, DCP-ClO demonstrated remarkable efficacy in monitoring ClO- levels in water samples and eye-catching ability in imaging endogenous/exogenous ClO- in living organisms, which verified its potential as a powerful tool for the recognition of ClO- in complex biological systems.

Conventional and machine-learning based risk score for patients with early-stage hepatocellular carcinoma.

Background/Aims: The performance of machine-learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups. Methods: The study retrospectively enrolled 1411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort. Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-to-monocyte ratio, and albumin bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATS-INF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores. Conclusions: Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

Passerini polymerization of α-lipoic acid for dynamically crosslinking 1,2-dithiolane-functionalized polymers.

Passerini polymerization using naturally occurring α-lipoic acid as a raw material yields polyamides with 1,2-dithiolane functional groups in a one-step reaction. The polyamide exhibits characteristics of an adaptable dynamically crosslinked network through reversible ring-opening reaction of 1,2-dithiolane, enabling self-healing, reusable strong adhesion, and regeneration through decrosslinking and re-crosslinking.

Regulation of Hard Segment Cluster Structures for High-performance Poly(urethane-urea) Elastomers.

Elastomers are widely used in daily life; however, the preparation of degradable and recyclable elastomers with high strength, high toughness, and excellent crack resistance remains a challenging task. In this report, a polycaprolactone-based poly(urethane-urea) elastomer is presented with excellent mechanical properties by optimizing the arrangement of hard segment clusters. It is found that long alkyl chains of the chain extenders lead to small and evenly distributed hard segment clusters, which is beneficial for improving mechanical properties. Together with the multiple hydrogen bond structure and stress-induced crystallization, the obtained elastomer exhibits a high strength of 63.3 MPa, an excellent toughness of 431 MJ m-3 and an outstanding fracture energy of 489 kJ m-2, while maintaining good recyclability and degradability. It is believed that the obtained elastomer holds great promise in various application fields and it contributes to the development of a sustainable society.

Targeting the MCP-GPX4/HMGB1 Axis for Effectively Triggering Immunogenic Ferroptosis in Pancreatic Ductal Adenocarcinoma.

Induction of ferroptosis can inhibit cancer cells in vitro, however, the role of ferroptosis in treatment in vivo is controversial. The immunosuppressive cells activated by the ferroptotic tumor cells can promote the growth of residual tumor cells, hindering the application of ferroptosis stimulation in tumor treatment. In this study, a new strategy is aimed to be identified for effectively triggering immunogenic ferroptosis in pancreatic ductal adenocarcinoma (PDAC) and simultaneously stimulating antitumor immune responses. Toward this, several molecular and biochemical experiments are performed using patient-derived organoid models and a KPC mouse model (LSL-KrasG12D /+, LSL-Trp53R172H/+, Pdx-1-Cre). It is observed that the inhibition of macrophage-capping protein (MCP) suppressed the ubiquitin fold modifier (UFM)ylation of pirin (PIR), a newly identified substrate of UFM1, thereby decreasing the transcription of GPX4, a marker of ferroptosis, and promoting the cytoplasmic transportation of HMGB1, a damage-associated molecular pattern. GPX4 deficiency triggered ferroptosis, and the pre-accumulated cytosolic HMGB1 is released rapidly. This altered release pattern of HMGB1 facilitated the pro-inflammatory M1-like polarization of macrophages. Thus, therapeutic inhibition of MCP yielded dual antitumor effects by stimulating ferroptosis and activating antitumor pro-inflammatory M1-like macrophages. The nanosystem developed for specifically silencing MCP is a promising tool for treating PDAC.

Matrix mechanics regulates muscle regeneration by modulating kinesin-1 activity.

Sarcopenia, a prevalent muscle disease characterized by muscle mass and strength reduction, is associated with impaired skeletal muscle regeneration. However, the influence of the biomechanical properties of sarcopenic skeletal muscle on the efficiency of the myogenic program remains unclear. Herein, we established a mouse model of sarcopenia and observed a reduction in stiffness within the sarcopenic skeletal muscle in vivo. To investigate whether the biomechanical properties of skeletal muscle directly impact the myogenic program, we established an in vitro system to explore the intrinsic mechanism involving matrix stiffness control of myogenic differentiation. Our findings identify the microtubule motor protein, kinesin-1, as a mechano-transduction hub that senses and responds to matrix stiffness, crucial for myogenic differentiation and muscle regeneration. Specifically, kinesin-1 activity is positively regulated by stiff matrices, facilitating its role in transporting mitochondria and enhancing translocation of the glucose transporter GLUT4 to the cell surface for glucose uptake. Conversely, the softer matrices significantly suppress kinesin-1 activity, leading to the accumulation of mitochondria around nuclei and hindering glucose uptake by inhibiting GLUT4 membrane translocation, consequently impairing myogenic differentiation. The insights gained from the in-vitro system highlight the mechano-transduction significance of kinesin-1 motor proteins in myogenic differentiation. Furthermore, our study confirms that enhancing kinesin-1 activity in the sarcopenic mouse model restores satellite cell expansion, myogenic differentiation, and muscle regeneration. Taken together, our findings provide a potential target for improving muscle regeneration in sarcopenia.

Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case report.

Introduction: Lynch syndrome is caused by a germline mutation in mismatch repair (MMR) genes, leading to the loss of expression of MMR heterodimers, either MLH1/PMS2 or MSH2/MSH6, or isolated loss of PMS2 or MSH6. Concurrent loss of both heterodimers is uncommon, and patients carrying pathogenic variants affecting different MMR genes are rare, leading to the lack of cancer screening recommendation for these patients.Case presentation:Here, we reported a female with a family history of Lynch syndrome with MLH1 c.676C > T mutation. She developed endometrial cancer at 37 years old, with loss of MLH1/PMS2 expression. Immunohistochemical staining on tumor samples incidentally detected the additional loss of MSH6 expression. Whole exome sequencing on genomic DNA from peripheral blood revealed MSH6 c.2731C > T mutation, which was confirmed to be inherited from her mother, who had an early-onset ascending colon cancer without cancer family history. Conclusion: This is a rare case of the Lynch syndrome harboring germline mutations simultaneously in two different MMR genes inherited from two families with Lynch syndrome. The diagnosis of endometrial cancer at the age less than 40 years is uncommon for Lynch syndrome-related endometrial cancer. This suggests an earlier cancer screening for patients carrying two MMR mutations.

Trivalent Phosphine-Catalyzed [4+1] Spiro-annulation Reaction Using Allenyl Imide and Methylene Cyclocompounds.

The trivalent phosphine-catalyzed [4+1] spiro-annulation reaction of allenyl imide and activated methylene cyclocompounds has been developed for the construction of various spiro-2-cyclopenten-1-ones. Oxindoles, 3-isochromanones, and 2-indanones are selected as 1C synthons to capture the in situ-generated bis-electrophilic α,ß-unsaturated ketenyl phosphonium intermediate, affording the corresponding monospiro- and bispiro-cyclopentenones in good to excellent yields (≤91%) under mild conditions. The primary attempt at asymmetric catalysis using monophosphine (R)-SITCP provides promising enantioselectivity (45% ee). A plausible reaction mechanism is also proposed.

Support for a hypothetical sugar-sweetened beverage tax in Taiwan.

Sugar-sweetened beverages (SSBs) are drinks that contain added sugar or sweeteners and provide calories with no additional nutrients, and some countries have imposed additional taxes on the SSBs to reduce consumption, which is considered an SSB tax policy. This study used a cross-sectional online survey to examine the patterns of public support for an SSB tax in Taiwan. The sample included 1617 adults aged ≥ 20 years, who answered the survey questionnaire between May 2020 and April 2021. The respondents were recruited using convenience sampling, but sampling weights were applied to represent the Taiwanese population. Generalized ordered logit models with sampling weights were used to examine the correlates of public support for an SSB tax. Results showed that ~60% of the respondents supported the SSB tax and 47% perceived the tax to be effective. The respondents who were aware of the perceived health risks of SSBs or those who believed that one should be partly responsible for the health impact of SSBs were more likely to show support for the SSB tax. In adjusted regression models, both one's perceived risk and perceived responsibility of SSBs were positively associated with the perceived effectiveness of the SSB tax after sociodemographic characteristics were controlled. These research findings show evidence that there is public support for implementing an SSB tax to reduce SSB consumption in Taiwan.

Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

The Impact of SARS-CoV-2 Infection on the Length of Stay in the Neuro-ICU:A Prospective Multicenter Cohort Study in Eight Neuro-ICU, China Between February and April 2023.

Purpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs. Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes. Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p>0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1-12) vs 4(1-8), p<0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p<0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death. Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients. Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.

An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of the Drosophila wing disc.

A programmed developmental switch to G / S endocycles results in tissue growth through an increase in cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute to cancer. Much remains unknown, however, about how these iECs affect tissue growth. Using the D. melanogasterwing disc as model, we find that populations of iECs initially increase in size but then subsequently undergo a heterogenous arrest that causes severe tissue undergrowth. iECs acquired DNA damage and activated a Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant and not eliminated from the epithelium. Instead, iECs entered a JNK-dependent and reversible senescent-like arrest. Senescent iECs promoted division of diploid neighbors, but this compensatory proliferation did not rescue tissue growth. Our study has uncovered unique attributes of iECs and their effects on tissue growth that have important implications for understanding their roles in wound healing and cancer.

Ulnar carpal translation following palmar locking plate fixation for distal radius fractures: a retrospective analysis.

BACKGROUND: Concomitant injuries to the radiocarpal ligaments may occur during episodes of distal radius fractures, which may not cause acute subluxation or dislocation but can lead to radiocarpal instability and progress over time. This study aimed to analyze the occurrence of ulnar carpal translation (UCT) after open reduction and internal fixation of distal radius fractures and evaluate the associated factors of UCT. METHODS: The retrospective study has been done now and includes patients treated between 2010 and 2020 who had undergone reduction and locking plate fixation of distal radius fractures. We assessed radiographs taken immediately after the operation and at 3 months post-operation, enrolling patients with UCT for evaluation. In addition to demographic data, we evaluated radiographic parameters, including fracture pattern, fragment involvement, and ulnar variance. We also assessed the palmar tilt-lunate (PTL) angle to determine associated rotatory palmar subluxation of the lunate (RPSL). RESULTS: Among the 1,086 wrists, 53 (4.9%) had UCT within 3 months post-operation. The majority of wrists with UCT exhibited normal to minus ulnar variance (49 wrists; mean: -1.1 mm), and 24 patients (45.3%) had concomitant RPSL. Fracture classification was as follows: 19 type A3 (35.8%), 5 type C1 (9.4%), 11 type C2 (20.8%), and 18 type C3 (34.0%). Radial styloid was involved in 20 wrists (37.7%), palmar rim in 18 wrists (34.0%), dorsal rim in 25 wrists (47.2%), and die-punch fractures in 3 wrists (5.7%). Concomitant ulnar styloid fractures were present in 29 wrists (54.7%). CONCLUSION: This study highlights the potential for UCT to occur following reduction and fixation of distal radius fractures, particularly in cases with a more severe fracture pattern and combined with ulnar minus variance. The high incidence of concomitant RPSL provides further evidence for the possibility of associated radiocarpal ligament insufficiency after distal radius fracture.