Mycobacterium marinum MMAR_0267-regulated copper utilization facilitates bacterial escape from phagolysosome.

The host limits Mycobacterium tuberculosis (Mtb) by enriching copper in high concentrations. This research investigates how Mtb escapes copper stress. The membrane protein encoded by Mtb Rv0102, when its homolog in M. smegmatis (MSMEG_4702) was knocked out, resulted in a fourfold decrease in intracellular copper levels and enhanced tolerance to elevated extracellular copper concentrations. Similarly, knockout mutants of its homolog in M. marinum (MMAR_0267) showed increased virulence in zebrafish and higher bacterial load within macrophages. In THP-1 cells infected with MMAR_0267 deletion mutants, the intracellular survival of these mutants increased, along with reduced THP-1 cell apoptosis. Deficiency in copper down-regulated the transcriptional level of the virulence factor CFP-10 in M. marinum, suppressed cytosolic signaling via the macrophage STING pathway, leading to decreased production of IFN-ß and reduced cell apoptosis. In conclusion, these findings highlight the significant impact of copper on the survival and reproduction of mycobacteria, underscoring the importance of studying mycobacterial adaptation mechanisms in copper-rich environments.

The synergistic effect of the atherogenic index of plasma and hyperuricemia on the prediction of coronary chronic total occlusion lesion: an observational cross-sectional study.

Background: The atherogenic index of plasma (AIP) and hyperuricemia (HUA) have been shown to be closely associated with morbidity and mortality of coronary artery disease. However, studies targeting predictive value of AIP and HUA for chronic total occlusion (CTO) lesions are still lacking. Methods: In total, 5,238 patients meeting the eligibility criteria were recruited in this analysis. CTO was defined as the condition of lesions without forward blood flow and with over three months of occlusion time. AIP was calculated as log10 [triglycerides (mmol/L)/high-density lipoprotein cholesterol (mmol/L)]. HUA was defined based on sex-specific criteria: serum uric acid 420 and 360 µmol/L for males and females, respectively. Results: CTO lesions were presented in 907 (17.3%) patients. Compared with patients showing lower AIP levels and non-HUA, the CTO lesion risks increased by 5.225 and 2.765 times in patients with higher AIP levels and HUA. Patients with AIP >0.15 and HUA exhibited the greatest CTO incidence (odds ratio 11.491; 95% confidence interval 9.019-14.641, P < 0.001). In addition, AIP combined with HUA had significantly increased effects (a 38.5% increase in CTO risk) relative to the sum of respective effects. Conclusion: Patients having higher AIP levels and HUA exhibited the highest CTO incidence, in comparison with patients who have the increased single index. AIP combined with HUA displayed significant synergistic effect on the prediction of CTO lesion.

Spatial Activation of Autophagy in Human Placenta-Related Tissue During Labor: A Possible Mechanism for Labor Onset.

INTRODUCTION: To explore the mechanisms of labor by investigating the autophagy of placental and fetal membranes tissue in normal pregnant women. METHODS: Placenta and fetal membranes were collected from women with singleton pregnancies without any medical complications and from women who delivered vaginally (labor-initiated group; L group) or by caesarean section (labor-noninitiated group; NL group). Autophagosomes were observed by transmission electron microscopy (TEM). Immunofluorescence and western blotting (WB) were used to detect protein levels of the autophagy markers LC3A and LC3B. TEM, immunohistochemistry (IHC), and WB were used to compare autophagy in different parts of the placenta and fetal membranes in the L and NL groups. The expression of LC3B/LC3A, ROCK1, and ROCK2 in the placenta of nonpregnant and pregnant rats was detected by WB and IHC. RESULTS: TEM and IHC results showed an increase in the number of autophagosomes and autophagic lysosomes in the L group, and WB results indicated an increase in the LC3B/A ratio between the placenta and fetal membranes in the L group. Autophagy was significantly increased on the maternal side of the placenta in the L group, and the level of autophagy became higher near rupture in the fetal membranes and near the point where the umbilical cord joins the placenta in the L group. The LC3B/A ratio increased and ROCK1 and ROCK2 levels decreased in postnatal rats. DISCUSSION: Autophagy can occur in the placenta and fetal membranes and its activity is higher at the onset of labor, suggesting a role in labor.

Application of a dual-modality colorimetric analysis method to inkjet printing lateral flow detection of Salmonella typhimurium.

Lateral flow assay (LFA) color signal quantification methods were developed by utilizing both International Commission on Illumination (CIE) LAB (CIELAB) color space and grayscale intensity differences. The CIELAB image processing procedure included calibration, test, control band detection, and color difference calculation, which can minimize the noise from the background. The LFA platform showcases its ability to accurately discern relevant colorimetric signals. The rising occurrence of infectious outbreaks from foodborne pathogens like Salmonella typhimurium presents significant economic, healthcare, and public health risks. The study introduces an aptamer-based lateral flow (ABLF) platform by using inkjet printing for specially detecting S. typhimurium. The ABLF utilized gold-decorated polystyrene microparticles, functionalized with specific S. typhimurium aptamers (Ps-AuNPs-ssDNA). The platform demonstrates a detection limit of 102 CFU mL-1 in buffer solutions and 103 CFU mL-1 in romaine lettuce tests. Furthermore, it sustained performance for over 8 weeks at room temperature. The ABLF platform and analysis methods are expected to effectively resolve the low-sensitivity problems of the former LFA systems and to bridge the gap between lab-scale platforms to market-ready solutions by offering a simple, cost-effective, and consistent approach to detecting foodborne pathogens in real samples.

The effect of hsCRP on TyG index-associated cardiovascular risk in patients with acute coronary syndrome undergoing PCI.

The effect of systemic inflammation, represented by high-sensitivity C-reactive protein (hsCRP), on triglyceride glucose (TyG) index-associated cardiovascular risk in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not yet been determined. This study was a retrospective analysis of a single-center prospective registry and finally included 1701 patients (age, 60 ± 10 years; male, 76.7%). The primary endpoint was defined as major adverse cardiovascular events (MACE), including cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarction. In the multivariate COX regression model that included the GRACE risk score, higher TyG index was significantly associated with a greater incidence of MACE in patients with hsCRP levels less than 2 mg/L but not 2 mg/L or more (P for interaction = 0.039). Each unit increase in the TyG index was independently associated with a 52% increased risk of MACE only in patients with hsCRP levels less than 2 mg/L (P = 0.021). After adjustment for other confounding factors, including the GRACE risk score, compared with those in the group of TyG index < 8.62 and hsCRP < 2 mg/L, patients in the group of TyG index ≥ 8.62 and hsCRP ≥ 2 mg/L had a 3.9 times higher hazard ratio for developing MACE. The addition of both TyG index and hsCRP had an incremental effect on the predictive ability of the GRACE risk score-based prognostic model for MACE (C-statistic: increased from 0.631 to 0.661; cNRI: 0.146, P = 0.012; IDI: 0.009, P < 0.001). In conclusion, there was a significant interaction between the TyG index and hsCRP for the risk of MACE, and the TyG index was reliably and independently associated with MACE only when hsCRP levels were less than 2 mg/L. Furthermore, high TyG index and high hsCRP levels synergistically increased the risk of MACE, suggesting that the prognostic value of TyG index combined with hsCRP might be promising in patients with ACS undergoing PCI.

Analysis of Factors Associated with Cough Persistence After Thoracoscopic Lung Cancer Resection in Elderly Lung Cancer Patients and Discussion of Prevention Strategies.

Objective: The aim was to investigate the factors associated with cough persistence after thoracoscopic lung cancer resection in elderly lung cancer patients and preventive strategies. Methods: In this study, 103 elderly patients with lung cancer who attended the department of thoracic surgery of our hospital from March 2019 to January 2023 were selected for retrospective analysis, all of whom underwent thoracoscopic lung cancer resection and were divided into the cough group (n = 37) and the no-cough group (n = 66) based on the presence or absence of persistent cough in the postoperative period. The clinical data of the patients were analyzed using univariate analysis and multifactorial logistic regression analysis. Results: The findings of the study show that there was no statistically significant difference when comparing the data of the two groups in terms of gender, age, history of diabetes mellitus, history of hypertension, pathologic type, TNM stage, intraoperative blood loss, and postoperative pleural fluid (P > .05). However, multifactorial analysis showed that preoperative history of smoking, the side of the operation being the right side, the extent of the operation being the lobes of the lungs, the time of tracheal intubation ≥172 min, the peritracheal lymph node clearance, and the occurrence of postoperative acid reflux were independent risk factors for the occurrence of persistent cough in patients after thoracoscopic lung cancer resection, while preoperative respiratory training was a protective factor (P < .05). Conclusion: There are many factors affecting persistent cough after thoracoscopic lung cancer resection. These factors need to be paid close attention to in the clinic and preventive measures should be taken to minimize the occurrence of persistent cough and promote postoperative recovery.

Hierarchical lncRNA regulatory network in early-onset severe preeclampsia.

BACKGROUND: Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. RESULTS: Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. CONCLUSIONS: Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.

Scalable Fabrication of Large-Scale, 3D, and Stretchable Circuits.

Stretchable electronics have demonstrated excellent potential in wearable healthcare and conformal integration. Achieving the scalable fabrication of stretchable devices with high functional density is the cornerstone to enable the practical applications of stretchable electronics. Here, a comprehensive methodology for realizing large-scale, 3D, and stretchable circuits (3D-LSC) is reported. The soft copper-clad laminate (S-CCL) based on the "cast and cure" process facilitates patterning the planar interconnects with the scale beyond 1 m. With the ability to form through, buried and blind VIAs in the multilayer stack of S-CCLs, high functional density can be achieved by further creating vertical interconnects in stacked S-CCLs. The application of temporary bonding substrate effectively minimizes the misalignments caused by residual strain and thermal strain. 3D-LSC enables the batch production of stretchable skin patches based on five-layer stretchable circuits, which can serve as a miniaturized system for physiological signals monitoring with wireless power delivery. The fabrications of conformal antenna and stretchable light-emitting diode display further illustrate the potential of 3D-LSC in realizing large-scale stretchable devices.

Combined effect of inflammation and malnutrition for long-term prognosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cohort study.

BACKGROUND: Inflammation is a key driver of atherosclerotic diseases and is often accompanied by disease-related malnutrition. However, the long-term burden of dysregulated inflammation with superimposed undernutrition in patients with acute coronary syndrome (ACS) remains unclear. This study sought to investigate the double burden and interplay of inflammation and malnutrition in patients with ACS undergoing percutaneous Coronary Intervention (PCI). METHODS: We retrospectively included 1,743 ACS patients undergoing PCI from June 2016 through November 2017 and grouped them according to their baseline nutritional and inflammatory status. Malnutrition was determined using the nutritional risk index (NRI) with a score lower than 100 and a high-inflamed condition defined as hs-CRP over 2 mg/L. The primary outcome was major adverse cardiovascular events (MACEs), compositing of cardiac mortality, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Long-term outcomes were examined using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding. The reclassification index (NRI)/integrated discrimination index (IDI) statistics estimated the incremental prognostic impact of NRI and hs-CRP in addition to the Global Registry of Acute Coronary Events (GRACE) risk score. RESULTS: During a median follow-up of 30 months (ranges 30-36 months), 351 (20.1%) MACEs occurred. Compared with the nourished and uninflamed group, the malnourished and high-inflamed group displayed a significantly increased risk of MACEs with an adjusted hazard ratio of 2.446 (95% CI: 1.464-4.089; P < 0.001). The prognostic implications of NRI were influenced by patients' baseline inflammatory status, as it was only associated with MACEs among those high-inflamed (P for interaction = 0.005). Incorporating NRI and hs-CRP into the GRACE risk score significantly improved its predictive ability for MACEs (NRI: 0.210, P < 0.001; integrated discrimination index; IDI: 0.010, P < 0.001) and cardiac death (NRI: 0.666, P < 0.001; IDI: 0.023, P = 0.002). CONCLUSIONS: Among patients with ACS undergoing PCI, the double burden of inflammation and malnutrition signifies poorer outcomes. Their prognostic implications may be amplified by each other and jointly improve the GRACE risk score's risk prediction performance.

Genome-Wide Identification, Expression and Response to Estrogen of Vitellogenin Gene Family in Sichuan Bream (Sinibrama taeniatus).

To enhance our understanding of teleost reproductive physiology, we identified six Sichuan bream (Sinibrama taeniatus) vitellogenin genes (vtg1-6) and characterized their sequence structures. We categorized them into type Ⅰ (vtg1,4,5 and 6), type Ⅱ (vtg2) and type Ⅲ (vtg3) based on differences in their subdomain structure. The promoter sequence of vtgs has multiple estrogen response elements, and their abundance appears to correlate with the responsiveness of vtg gene expression to estrogen. Gene expression analyses revealed that the vitellogenesis of Sichuan bream involves both heterosynthesis and autosynthesis pathways, with the dominant pathway originating from the liver. The drug treatment experiments revealed that 17ß-estradiol (E2) tightly regulated the level of vtg mRNA in the liver. Feeding fish with a diet containing 100 µg/g E2 for three weeks significantly induced vtg gene expression and ovarian development, leading to an earlier onset of vitellogenesis. Additionally, it was observed that the initiation of vtg transcription required E2 binding to its receptor, a process primarily mediated by estrogen receptor alpha in Sichuan bream. The findings of this study provide novel insights into the molecular information of the vitellogenin gene family in teleosts, thereby contributing to the regulation of gonadal development in farmed fish.

Investigating the role of TGF-ß and BDNF in cancer-related depression: a primary cross-sectional study.

BACKGROUND: Cancer-related depression is a well-documented condition that significantly impacts long-term quality of life. Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neurogenesis and neuronal plasticity, has been implicated in various neuropsychological disorders including depression associated with cancer. Cytokines, on the other hand, play a crucial role in regulating depression, potentially by influencing BDNF expression. Transforming growth factor-ß (TGF-ß), a key immune regulator within the tumor microenvironment, has been found to elevate BDNF levels, establishing a link between peripheral immune responses and depression. The study aims to investigate the correlation of TGF-ß and BDNF in cancer-related depression. METHODS: This study involved a cohort of 153 gynecological patients, including 61 patients with gynecological cancer and 92 patients without cancer. Depression levels were assessed using the subscale of Hospital Anxiety and Depression Scale (HADS-D), and TGF-ß and BDNF plasma levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The study revealed elevated plasma TGF-ß levels in patients with cancer (32.24 ± 22.93 ng/ml) compared to those without cancer (25.24 ± 19.72 ng/ml) (P = 0.046). Additionally, reduced levels of BDNF were observed in patients presenting depression symptoms (44.96 ± 41.06 pg/ml) compared to those without depression (133.5 ± 176.7 pg/ml) (P = 0.036). Importantly, a significant correlation between TGF-ß and BDNF was found in patients without cancer but with depression (correlation coefficient = 0.893, **P < 0.01). Interestingly, cancer appeared to influence the association between TGF-ß and BDNF in patients with depression, as evidenced by a significant difference in the correlation of TGF-ß and BDNF between cancer and non-cancer groups (P = 0.041). CONCLUSIONS: These findings underscore the active involvement of TGF-ß and BDNF crosstalk in the context of cancer-related depression.

A Multimodal Self-Propelling Tensegrity Structure.

Tensegrity structure is composed of tensile cables and compressive rods, offering high stiffness-to-mass ratio, deploy ability, and excellent energy damping capability. The active and dynamic tensegrity designs demonstrate great potential for soft robots. In previous designs, the movement has relied on carefully controlled input power or manually controlled light irradiation, limiting their potential applications. Here, a hybrid tensegrity structure (HTS) is constructed by integrating thermally responsive cables, nonresponsive cables, and stiff rods. The HTS can self-propel continuously on a hot surface due to its unique geometry. The HTS allows for the easy achievement of multimodal self-propelled locomotive modes, which has been challenging for previously demonstrated self-propelling structures. Additionally, using Velcro tapes to adhere the rods and cables together, a modulable and reassemblable HTS is created. The HTS introduced in this study presents a new strategy and offers a large design space for constructing self-propelling and modulable robots.

Effect of low-intensity focused ultrasound therapy on postpartum uterine involution in puerperal women: A randomized controlled trial.

BACKGROUND: Short-term poor uterine involution manifests as uterine contraction weakness. This is one of the important causes of postpartum hemorrhage, posing a serious threat to the mother's life and safety. The study aims to investigate whether low-intensity focused ultrasound (LIFUS) can effectively shorten lochia duration, alleviate postpartum complications, and accelerate uterine involution compared with the sham treatment. METHODS: A multicenter, concealed, randomized, blinded, and sham-controlled clinical trial was conducted across three medical centers involving 176 subjects, utilizing a parallel group design. Enrollment occurred between October 2019 and September 2020, with a 42-day follow-up period. Participants meeting the inclusion and exclusion criteria based on normal prenatal examinations were randomly divided into the LIFUS group or the sham operation group via computer-generated randomization. Patients in the LIFUS group received usual care with the LIFUS protocol, wherein a LIFUS signal was transmitted to the uterine site through coupling gel, or sham treatment, where no low-intensity ultrasound signal output was emitted. The primary outcome, lochia duration, was assessed via weekly telephonic follow-ups post-discharge. The involution of the uterus, measured by uterine fundus height, served as the secondary outcome. RESULTS: Among the 256 subjects screened for eligibility, 176 subjects were enrolled and randomly assigned to either the LIFUS group (n = 88) or the Sham group (n = 88). Data on the height of the uterine fundus were obtained from all the patients, with 696 out of 704 measurements (99%) successfully recorded. Overall, a statistically significant difference was noted in time to lochia termination (hazard ratio: 2.65; 95% confidence interval [CI]: 1.82-3.85; P < 0.001). The decline in fundal height exhibited notable discrepancies between the two groups following the second treatment session (mean difference: -1.74; 95% CI: -1.23 to -2.25; P < 0.001) and the third treatment session (mean difference: -3.26; 95% CI: -2.74 to -3.78; P < 0.001) after delivery. None of the subjects had any adverse reactions, such as skin damage or allergies during the treatment. CONCLUSIONS: This study found that LIFUS treatment can promote uterine involution and abbreviate the duration of postpartum lochia. Ultrasound emerges as a safe and effective intervention, poised to address further clinical inquiries in the domain of postpartum rehabilitation.

Synthesis of Double Trivalent Perovskite Quantum Dots Cs3BiSbX9 (X = Cl, Br, I) for Efficient CO2 Photoreduction Performance.

Non-toxic Bi halides have great potential in the field of CO2 photoreduction, but strong charge localization limits their charge separation and transfer. In this study, a series of Cs3BiSbX9 (X = Cl, Br, I) perovskite quantum dots (PQDs) are synthesized by antisolvent recrystallization at room temperature, in which Cs3BiSbBr9 PQDs has high selectivity (94.51%) and yield (15.32 µmol g-1 h-1) of CO2 to CO. In situ DRIFTS and theoretical calculations suggest that the surface charge can be tailored by halogen modulation, allowing for the customization of intermediate species. The Bi─Br─Sb symmetric charge distribution induced by the halogen Br promotes the formation of b─HCOO and reduces the reaction energy barrier of the rate-limiting step, while the weak electronegativity of Cl and the high electronegativity of I leads to m─HCOO and ─COOH production, which are detrimental to CO generation. This work provides new insights into the design of halide alloy perovskites for CO2 photoreduction.

Uncovering the selectivity mechanism of phosphodiesterase 7A/8A inhibitors through computational studies.

The expression of phosphodiesterase 7A (PDE7A) and phosphodiesterase 8A (PDE8) genes is integral to human signaling pathways, and the inhibition of PDE7A has been associated with the onset of various diseases, including effects on the immune system and nervous system. The development of PDE7 selective inhibitors can promote research on immune and nervous system diseases, such as multiple sclerosis, chronic inflammation, and autoimmune responses. PDE8A is expressed alongside PDE8B, and its inhibitory mechanism is still unclear. Studying the mechanisms of selective inhibitors against different PDE subtypes is crucial to prevent potential side effects, such as nausea and cardiac toxicity, and the sequence similarity of the two protein subtypes was 55.9%. Therefore, it is necessary to investigate the differences of both subtypes' ligand binding sites. Selective inhibitors of two proteins were chosen to summarize the reason for their selectivity through molecular docking, molecular dynamics simulation, alanine scanning mutagenesis, and MM-GBSA calculation. We found that Phe384PDE7A, Leu401PDE7A, Gln413PDE7A, Tyr419PDE7A, and Phe416PDE7A in the active site positively contribute to the selectivity towards PDE7A. Additionally, Asn729PDE8A, Phe767PDE8A, Gln778PDE8A, and Phe781PDE8A positively contribute to the selectivity towards PDE8A.

Value of Absolute Eosinophil Count in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background and Aims: Elevated eosinophils typically indicate hypersensitive inflammation; however, their involvement in cardiovascular events remains incompletely understood. We investigated the association between the absolute eosinophil count (AEC) and major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Additionally, we determine whether the integration of AEC with the SYNTAX II score could improve predictive ability. Methods and Results: The AECs of 1711 patients with ACS undergoing PCI from June 2016 to November 2017 were analyzed on admission. All recruitments were splitted into three groups based on AEC tertiles and 101 participants underwent one or more noteworthy outcomings. The association between AEC and MACCEs (defined as a composite of cardiovascular death, myocardial infarction [MI], and stroke) was tested by Cox proportional-hazards regression analysis. After adjusting for confounders, AEC was independently associated with MACCEs (HR 11.555, 95% CI: 3.318-40.239). Patients in the lowest AEC tertile (T1) as a reference, those in the higher tertiles had an incrementally higher risk of MACCEs (T3: HR 1.848 95% CI: 1.157-2.952; P for trend=0.008). Inclusion of AEC enhanced the predictive accuracy of the SYNTAX II score for MACCEs (AUC: from 0.701 [95% CI: 0.646-0.756] to 0.728 [95% CI: 0.677-0.780]; DeLong's test, P = 0.020). Conclusion: AEC is independently linked to MACCEs in ACS patients who underwent PCI, and adds incremental predictive information to the SYNTAX II score.

Insights into the selective mechanism of PDE2/9a inhibitors from silico aspects.

The selective design of competitive enzyme inhibitors is an extremely difficult task but necessary work for certain types of systems, such as the phosphodiesterase (PDE) system addressed in this article. In the PDE family, PDE2A and PDE9 respectively target the central nervous system and heart failure, and share many conserved amino acids at their binding sites. Therefore, gaining a deep understanding of the selective mechanisms of PDE2A/9A is crucial for designing highly selective drugs. In this study, various computer-aided drug design (CADD) methods, including molecular docking, molecular dynamics simulations (MD), and binding free energy calculations, are employed to explore the selective mechanisms of PDE2A/9A. Overall, our research results indicate a selective design strategy for PDE2A, which involves incorporating hydrophobic or aromatic moieties into the molecular structure to better accommodate the hydrophobic pocket of PDE2A. Additionally, it is recommended to introduce functional groups capable of forming connections with selective residues, such as Phe830 and Gln812 for PDE2A, or Ala452 and Tyr424 for PDE9A, to enhance the selectivity of inhibitors targeting PDE2A/9A. This achievement is anticipated to pave the way for the development of innovative and selective small molecules targeting PDE2A/9A.Communicated by Ramaswamy H. Sarma.

Impact of Climate Change on the Distribution of Three Rare Salamanders (Liua shihi, Pseudohynobius jinfo, and Tylototriton wenxianensis) in Chongqing, China, and Their Conservation Implications.

The Wushan Salamander (Liua shihi), Jinfo Salamander (Pseudohynobius jinfo), and Wenxian Knobby Salamander (Tylototriton wenxianensis) are rare national Class II protected wild animals in China. We performed MaxEnt modeling to predict and analyze the potential distribution and trends of these species in Chongqing under current and future climate conditions. Species distribution data were primarily obtained from field surveys, supplemented by museum collections and the existing literature. These efforts yielded 636 records, including 43 for P. jinfo, 23 for T. wenxianensis, and 570 for L. shihi. Duplicate records within the same 100 m × 100 m grid cell were removed using ENMTools, resulting in 10, 12, and 58 valid distribution points for P. jinfo, T. wenxianensis, and L. shihi, respectively. The optimization of feature class parameters (FC) and the regularization multiplier (RM) were applied using R package "ENMeval 2.0" to establish the optimal model with MaxEnt. The refined models were applied to simulate the suitable distribution areas for the three species. The results indicate that the current suitable habitat area for L. shihi accounted for 9.72% of the whole region of the Chongqing municipality. It is projected that, by 2050, the proportion of suitable habitat will increase to 12.54% but will decrease to 11.98% by 2070 and further decline to 8.80% by 2090. The current suitable habitat area for P. jinfo accounted for 1.08% of the whole region of the Chongqing municipality, which is expected to decrease to 0.31%% by 2050, 0.20% by 2070, and 0.07% by 2090. The current suitable habitat area for T. wenxianensis accounted for 0.81% of the whole region of the Chongqing municipality, which is anticipated to decrease to 0.37% by 2050, 0.21% by 2070, and 0.06% by 2090. Human disturbance, climate variables, and habitat characteristics are the primary factors influencing the distribution of three salamander species in Chongqing. The proximity to roads significantly impacts L. shihi, while climate conditions mainly affect P. jinfo, and the distance to water sources is crucial for T. wenxianensis. The following suggestions were made based on key variables identified for each species: (1) For L. shihi, it is imperative to minimize human disturbances and preserve areas without roads and the existing vegetation within nature reserves to ensure their continued existence. (2) For P. jinfo, the conservation of high-altitude habitats is of utmost importance, along with the reduction in disturbances caused by roads to maintain the species' ecological niche. (3) For T. wenxianensis, the protection of aquatic habitats is crucial. Additionally, efforts to mitigate the impacts of road construction and enhance public awareness are essential for the preservation of this species and the connectivity of its habitats.

Mechanochromic Hydrogel Fibers with Multiple Fluorescent Colors.

Mechanochromic polymers can change their color in response to external force and have shown promising applications in stress sensing and failure warning. They are usually obtained as thin films or bulky specimens. The mechanochromic fibers, which can be used to make smart fabrics, have been seldom reported due to the lack of efficient fabrication techniques. In this work, a general method using photo-polymerization of microgel solution in a template tube to produce mechanochromic hydrogel fibers is reported. The obtained hydrogel fibers can generate visible and fluorescent color changes upon deformation. The diameter of the mechanochromic fibers can be easily adjusted by using different template tubes. The mechanochromic fibers can be fabricated as long as 1 m. By reducing the fiber diameter or increasing the microgel concentration, the mechanical properties of the mechanochromic fibers can be improved, leading to more obvious mechanochromic behavior. The polymethacrylate (PMA) is further used to coat the hydrogel fibers, prevent the loss of water in the fibers, and increase the storage time. The mechanochromic fibers with multiple fluorescent colors are further fabricated by utilizing different microgel solutions. This work provides an easy and effective method to fabricate mechanochromic fibers with different color change abilities.