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Societal Impact Statement Unraveling the genetic intricacies and evolutionary history of Asian Hickories through advanced genome sequencing gives valuable insights into their ecological adaptations. Understanding the impact of historical dynamics, climate fluctuations, and geographical barriers on Asian hickories not only contributes to scientific knowledge but also empowers policymakers with evidence‐based decisions and guides conservationists in their efforts to protect vulnerable species. The identification of potential habitats, especially for the endangered Carya kweichowensis, offers a promising avenue for targeted conservation efforts, aligning with global initiatives to preserve Earth's precious biodiversity, but also ensures the conservation of a vital genetic reservoir for nut‐bearing economic tree species. Summary Biogeographic characteristics of disjunct distribution play a vital role in plant geography and the endangered mechanism. The whole genome resequencing provides an opportunity to study the genetic relationship, population diffusion, and floristic evolution of disjunctive‐distribution flora. Based on the SNPs (single nucleotide polymorphisms) data generated by the whole genome deep resequencing of five EA (Eastern Asian) Carya species, we constructed the phylogenetic tree, genetic structure, and species distribution modeling to clarify the phylogenetic relationships and to predict the potential distribution area of EA Carya. Phylogenetic analysis of Carya revealed two distinct clades, separating EA Carya from NA (North America) Carya. C. kweichowensis, an endangered species, showed the lowest nucleotide diversity and the earliest divergence among studied EA Carya species. Species distribution modeling predicted suitable habitats for five EA Carya species, revealing the potential distribution of endangered C. kweichowensis. Importantly, minimal spatial overlap was observed among distribution regions of EA Carya species during different time periods. The uneven regional distribution of EA Carya is believed to be a consequence of Quaternary climate fluctuations, mountain barriers hindering species dispersal, and the limited cold tolerance of these trees. EA Carya highlights the significant role of climate and geological changes in their regional distribution and migration routes in Asia. Furthermore, the discovery of potential habitats offers a promising avenue for the conservation of C. kweichowensis.

Objectives: Intrinsic capacity (IC), a multidimensional construct encompassing mental and physical capacities, has been established in the aging framework by the World Health Organization. However, the detailed relationship between IC and Chinese sleep patterns (nighttime sleep and post-lunch naps) remains inadequately elucidated. Methods: Participants in this study were individuals aged ≥45 years residing in China, included in the China Health and Retirement Longitudinal Study (CHARLS). We analyzed 4 years of CHARLS data from the first wave (May 2011–March 2012) to the second wave (July 2015–January 2016). Data from these waves were utilized for longitudinal analysis. Self-reported data included nighttime sleep and nap duration, along with other baseline characteristics. The IC evaluation involved physical examinations and blood tests. Initially, linear regression was used to assess the relationship between total sleep duration, nighttime sleep duration, nap duration, and IC change between the two waves that were determined by marginal effects (ME) and their corresponding 95% confidence intervals (CIs). Regression splines were employed to explore potential nonlinear associations. Subgroup and sensitivity analyses were conducted to investigate the heterogeneity of IC change under specific conditions and the robustness of our results. Mediation analysis was performed to identify potential factors mediating the relationship between sleep patterns and IC change. Results: Both excessive (>10 h) (total, ME: −1.12; 95% CI: −1.61, −0.64; nighttime, ME: −1.44; 95% CI: −2.29, −0.59) and insufficient (

ObjectivesTo apply machine learning to extract radiomics features from thyroid two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasound (CEUS) images to classify and predict benign and malignant thyroid nodules, classified according to the Chinese version of the thyroid imaging reporting and data system (C-TIRADS) as category 4.Materials and methodsThis retrospective study included 313 pathologically diagnosed thyroid nodules (203 malignant and 110 benign). Two 2D-US images and five CEUS key frames (“2nd second after the arrival time” frame, “time to peak” frame, “2nd second after peak” frame, “first-flash” frame, and “second-flash” frame) were selected to manually label the region of interest using the “Labelme” tool. A total of 7 images of each nodule and their annotates were imported into the Darwin Research Platform for radiomics analysis. The datasets were randomly split into training and test cohorts in a 9:1 ratio. Six classifiers, namely, support vector machine, logistic regression, decision tree, random forest (RF), gradient boosting decision tree and extreme gradient boosting, were used to construct and test the models. Performance was evaluated using a receiver operating characteristic curve analysis. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), and F1-score were calculated. One junior radiologist and one senior radiologist reviewed the 2D-US image and CEUS videos of each nodule and made a diagnosis. We then compared their AUC and ACC with those of our best model.ResultsThe AUC of the diagnosis of US, CEUS and US combined CEUS by junior radiologist and senior radiologist were 0.755, 0.750, 0.784, 0.800, 0.873, 0.890, respectively. The RF classifier performed better than the other five, with an AUC of 1 for the training cohort and 0.94 (95% confidence interval 0.88–1) for the test cohort. The sensitivity, specificity, accuracy, PPV, NPV, and F1-score of the RF model in the test cohort were 0.82, 0.93, 0.90, 0.85, 0.92, and 0.84, respectively. The RF model with 2D-US combined with CEUS key frames achieved equivalent performance as the senior radiologist (AUC: 0.94 vs. 0.92, P = 0.798; ACC: 0.90 vs. 0.92) and outperformed the junior radiologist (AUC: 0.94 vs. 0.80, P = 0.039, ACC: 0.90 vs. 0.81) in the test cohort.ConclusionsOur model, based on 2D-US and CEUS key frames radiomics features, had good diagnostic efficacy for thyroid nodules, which are classified as C-TIRADS 4. It shows promising potential in assisting less experienced junior radiologists.

Abstract Background Cyclin‐dependent kinases 4 and 6 inhibitors (CDK4/6i) have been shown to improve progression‐free survival (PFS) in patients with metastatic breast cancer (MBC) in randomized control trials. This study aimed to evaluate the efficacy and safety of CDK4/6i in patients with advanced breast cancer (ABC) in a clinical setting. Methods Consecutive patients with ABC were treated between October 2019 and March 2023 at Taipei Tzu Chi Hospital, Taiwan. Patients who had received at least one dose of CDK4/6i were included in this retrospective study. The main outcome of this study was efficacy based on the treating physicians' assessments in terms of PFS, and overall survival (OS), as well as the factors associated with patient outcome. The secondary outcome was safety. Results A total of 85 patients were included in the analysis, with a mean age of 66.8 years. After a median follow‐up of 16.1 months, the median PFS was 28.4 months (95% CI: 22.5–33.6) and the median OS could not yet be estimated. The most common adverse events (AE) were fatigue (50.8%), anorexia (45.9%), and leukopenia (44.7%). In multivariable analysis, treatment with CDK4/6i with any grade AE or response to treatment effect (CR/PR) was an independent predictor for longer PFS (hazard ratio [HR] = 0.27, 95% CI: 0.11–0.68; HR = 0.21, 95% CI: 0.06–0.67; p

Summary: Huntington’s disease (HD) usually causes cognitive disorders, including learning difficulties, that emerge before motor symptoms. Mutations related to lysosomal trafficking are linked to the pathogenesis of neurological diseases, whereas the cellular mechanisms remain elusive. Here, we discover a reduction in the dendritic density of lysosomes in the hippocampus that correlates with deficits in synaptic plasticity and spatial learning in early CAG-140 HD model mice. We directly manipulate intraneuronal lysosomal positioning with light-induced CRY2:CIB1 dimerization and demonstrate that lysosomal abundance in dendrites positively modulates long-term potentiation of glutamatergic synapses onto the neuron. This modulation depends on lysosomal Ca2+ release, which further promotes endoplasmic reticulum (ER) entry into spines. Importantly, optogenetically restoring lysosomal density in dendrites rescues the synaptic plasticity deficit in hippocampal slices of CAG-140 mice. Our data reveal dendritic lysosomal density as a modulator of synaptic plasticity and suggest a role of lysosomal mispositioning in cognitive decline in HD.

Abstract Arbuscular mycorrhizal fungi (AMF) that establish reciprocal symbiosis with plant roots can enhance resistance to various stresses, including salt stress, but relevant mechanisms, especially at the molecular level, are scarce. The objective of this study was to analyze the effect of an arbuscular mycorrhizal fungus Paraglomus occultum on plant growth, leaf gas exchange, and expression of plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs) and salt overly sensitive (SOS) genes in tomato under salt (150 mmol/L NaCl) and non-salt stress. Salt stress for 4 weeks inhibited root colonization rate of P. occultum and soil hyphal length by 0.21- and 0.57-fold, respectively. Salt stress also inhibited plant growth performance and leaf gas exchange, while inoculation with P. occultum significantly enhanced them under salt and non-salt stress conditions. AMF showed diverse regulation of root SlPIPs and SlTIPs expression, among which under salt stress, SlPIP1;2, SlPIP1;5, SlPIP2;1, SlPIP2;6, SlPIP2;9, SlPIP2;10, SlTIP2;2, SlTIP3;2, and SlTIP5;1 were up-regulated by AMF colonization, and SlPIP1;7, SlPIP2;5, SlPIP2;8, SlPIP2;11, SlPIP2;12, SlTIP2;3, and SlTIP3;1 were down-regulated, accompanied by no change in SlPIP1;1, SlPIP1;3, SlPIP2;4, SlTIP1;1, SlTIP1;2, SlTIP1;3, SlTIP2;1, and SlTIP2;5. Interestingly, salt stress inhibited the expression of SlSOS1 and SlSOS2 in non-mycorrhizal plants, while it increased the expression of SlSOS1 and SlSOS2 in mycorrhizal plants. AMF colonization down-regulated expression of SlSOS1 and SlSOS2 under non-salt stress while up-regulated expression of SlSOS1 and SlSOS2 under salt stress. It was concluded that AMF inoculation impacted the expression of stress-responsive genes, especially SOS1 and SOS2, and enhanced salt resistance of tomato. Graphical Abstract

Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission.

Culture substrates display profound influence on biological and developmental characteristic of cells cultured in vitro. This study investigates the influence of polyvinyl alcohol (PVA) substrates blended with different concentration of collagen or/and gelatin on the cell adhesion, proliferation, shape, spreading, and differentiation of stem cells. The collagen/gelatin blended PVA substrates were prepared by air drying. During drying, blended collagen or/and gelatin can self-assemble into macro-scale nucleated particles or branched fibrils in the PVA substrates that can be observed under the optical microscope. These collagen/gelatin blended substrates revealed different surface topography, z-average, roughness, surface adhesion and Young’s modulus as examined by the atomic force microscope (AFM). The results of Fourier transform infrared spectroscopy (FTIR) analysis indicated that the absorption of amide I (1,600–1,700 cm−1) and amide II (1,500–1,600 cm−1) groups increased with increasing collagen and gelatin concentration blended and the potential of fibril formation. These collagen or/and gelatin blended PVA substrates showed enhanced NIH-3T3 fibroblast adhesion as comparing with the pure PVA, control tissue culture polystyrene, conventional collagen-coated and gelatin-coated wells. These highly adhesive PVA substrates also exhibit inhibited cell spreading and proliferation. It is also found that the shape of NIH-3T3 fibroblasts can be switched between oval, spindle and flattened shapes depending on the concentration of collagen or/and gelatin blended. For inductive differentiation of stem cells, it is found that number and ration of neural differentiation of rat cerebral cortical neural stem cells increase with the decreasing collagen concentration in the collagen-blended PVA substrates. Moreover, the PVA substrates blended with collagen or collagen and gelatin can efficiently support and conduct human pluripotent stem cells to differentiate into Oil-Red-O- and UCP-1-positive brown-adipocyte-like cells via ectodermal lineage without the addition of mitogenic factors. These results provide a useful and alternative platform for controlling cell behavior in vitro and may be helpful for future application in the field of regenerative medicine and tissue engineering.

Objectives: Circulating microRNAs (miRNAs) have been discovered to play a novel role in intercellular communication and cancer biology. They are emerging candidates for noninvasive molecular biomarkers of cancer and other diseases. However, current translational researches have been limited by the lack of consensus on the optimal endogenous control of circulating miRNAs quantitation. In this study, we compared two promising miRNAs, miR-1228 and miR-16, as an endogenous control. The effects of normalizers on the relative quantification of circulating miR-31 in plasma samples of colorectal cancer (CRC) were also assessed. Materials and Methods: The cel-miR-39 was a spiked-in RNA used as an external control and added to plasma samples before RNA extraction. Quantitative real-time polymerase chain reaction technology was used to analyze the expression levels of circulating miRNAs in plasma samples of 4 healthy controls and 14 CRC patients. The expression stability of the candidate controls was compared by Ct analysis and NormFinder algorithms. Results: There was no significant difference in expression level of miR-16 and miR-1228 between healthy control group and before or after therapy of CRC patient groups. The expression of miR-1228 has smaller the range Ct values (28.25-25.64) compared with those of miR-16 (24.91-20.34). The stability value of miR-1228 (0.102) is lower than that of miR-16 (0.350). The expression of miR-1228 endogenous reference candidate has lower stability value and smaller the range Ct values compared with those in miR-16. According to the range Ct values and stability value, miR-1228 is better than miR-16 as endogenous control in CRC patients. There are significant differences in circulating miR-31 expression between healthy control and CRC patients when miR-1228 was used to standardize miR-31 expression. Conclusions: miR-1228 is recommended as a better endogenous control in quantification of circulating miRNAs in CRC patients.

AIM: To investigate whether the axial length (AL)/total corneal refractive power (TCRP) ratio is a sensitive and simple factor that can be used for the early diagnosis of Marfan's syndrome (MFS) in children. METHODS: The relationship between the AL/TCRP ratio and the diagnosis of MFS for 192 eyes in 97 children were evaluate. The biological characteristics, including age, sex, AL, and TCRP, were collected from medical records. Receiver operating characteristic (ROC) curve analysis was performed to investigate whether the AL/TCRP ratio effectively distinguishes MFS from other subjects. The Youden index was used to re-divide the whole population into two groups according to an AL/TCRP ratio of 0.59. RESULTS: Of 96 subjects (mean age 7.46±3.28y) evaluated, 56 (110 eyes) had a definite diagnosis of MFS in childhood based on the revised Ghent criteria, 41 (82 eyes) with diagnosis of congenital ectopia lentis (EL) were included as a control group. AL was negatively correlated with TCRP, with a linear regression coefficient of -0.36 (R2=0.08). A significant correlation was found between age and the AL/TCRP ratio (P=0.023). ROC curve analysis showed that the AL/TCRP ratio distinguished MFS from the other patients at a threshold of 0.59. MFS patients were present in 24/58 (41.38%) patients with an AL/TCRP ratio of ≤0.59 and in 34/39 (87.18%) patients with an AL/TCRP ratio of >0.59. CONCLUSION: An AL/TCRP ratio of >0.59 is significantly associated with the risk of MFS. The AL/TCRP ratio should be measured as a promising marker for the prognosis of children MFS. Changes in the AL/TCRP ratio should be monitored over time.

Although the approach of forming an ultrahigh-Q nanocavity via local refractive index tuning in a PC waveguide was proposed a decade ago, it has not yet been employed to realize a moveable ultrahigh-Q nanocavity, thereby the dynamic physics related to a moving resonator remain unknown. Here we demonstrate that a dynamically-formed cavity is essentially moveable, so that we can use this nanocavity to trap, store, and transfer signal photons, enabling free photon control. For a high cavity moving speed, we find the trapped signal energy will radiate out of the moving cavity. We think this interesting phenomenon originates from Doppler-effect-induced resonant frequency split in a moving resonator and the accompanied change of energy capacity. In addition, we present an analytical model to reveal why and how the trapping and storing processes are accompanied by significant spectral bandwidth compression and dynamic wavelength conversion, which are critical for achieving dynamic ultrahigh-Q nanocavity. This approach may find application in photon memories, quantum computing, and controllable light-matter interactions.

Objective: The current study aimed to retrospectively assess the cancer detection rate of needle localization biopsy of breast microcalcifications undetectable on sonography. Materials and Methods: Patients who underwent mammography-guided needle localization biopsy of breast microcalcifications undetectable on sonography from January 2005 to December 2017 were included in the study. Patients with incomplete medical records were excluded from the study. Patient mammograms were categorized using the Breast Imaging-Reporting and Data System (BI-RADS) assessment criteria. The percentages of benign and malignant lesions were determined by pathological examination of surgically recovered specimens. Correlation between preoperative imaging assessment and final diagnosis was investigated, and the complications associated with the procedures were recorded. Results: A total of 301 needle-localized biopsies were performed under mammographic guidance. The mean age of the patients was 58.18 ± 7.73 years. The overall ductal carcinoma in situ (DCIS) and cancer detection rate was 23.3%. The proportion of patients with BI-RADS 0 category and undergoing second mammography was higher in the DCIS and cancer group. A total of 227 patients did not undergo second mammography. Of these patients, 70 demonstrated BI-RADS 4 category, 34 were diagnosed with DCIS, and 5 were diagnosed with breast cancer during subsequent follow-up. Conclusion: Needle-localized excision of microcalcifications undetectable on sonography has high detection rate for early stage of breast cancer with low risk of associated complications. Regular mammography is a satisfactory follow-up tool for female patients with microcalcifications in the breasts. Additional studies should be performed to compare between needle-localized excision and vacuum-assisted breast biopsy.

Hickory (Carya cathayensis) kernel is rich in powerful bioactive flavonoids, which can remove excess free radicals in the human body and play an important role in regulating the physiological metabolism of the plant. This study investigated the changes of flavonoids in hickory exocarp and embryo during development. In this study, 72 DEGs involved in the regulation of flavonoid biosynthesis in fruits were identified, and TT4, CCoAOMT1, UGT71D1, C4H, F3H, TT8, FLS1, and LDOX were identified as the core genes of flavonoid biosynthesis. A total of 144 flavonoid-related metabolites were detected by metabolite analysis. Transcriptome and metabolome analysis combined to construct the flavonoid biosynthesis regulatory pathway in the development stage of hickory fruit. Our results provide a theoretical basis for the exploration and regulation of functional genes related to flavonoid biosynthesis and metabolism in hickory and other plants and the breeding of new walnut varieties.

ObjectiveThe aim of this study was to examine the biometric ocular manifestations and structural ocular features of anterior megalophthalmos (AM).MethodsFifteen patients with AM (30 eyes) from the Eye & ENT Hospital of Fudan University were included. The age-matched control group consisted of 30 participants (30 eyes) who underwent Pentacam HR and IOLMaster 700 measurements for one normal eye. Data on demographics, biometric manifestations, and genotypes were carefully compared.ResultsA total of 15 patients with AM and 30 control patients were enrolled. There were no differences in age (37.27 ± 19.1 vs. 31.43 ± 19.69 years, P = 0.249) between these two groups. AM eyes were characterized by premature cataracts (11/30, 36.67%) and zonular weakness with lens subluxation (22/30, 73.33%) compared with the control group. Notably, 20 of the 30 AM eyes (66.67%) had significant posterior iris bowing, and 16 of the 30 AM eyes (53.33%) showed an enlarged ciliary ring on ultrasound biomicroscopy (UBM). Mean corneal curvature was lower in the AM eyes (42.01 ± 2.06 D vs. 43.14 ± 1.38 D, P = 0.023). There was no significant difference in corneal pachymetry and central endothelial cell count between the AM and control groups. Significant differences were found in terms of the anterior chamber and white-to-white (WTW) among the Pentacam HR and IOLMaster 700 in patients with AM (P < 0.05). The difference was 0.53 ± 0.48 mm and 0.36 ± 0.14 mm, respectively (P < 0.001).ConclusionThe results of this cohort study conclude the biometric and structural ocular manifestations in Chinese cohorts. Posterior iris bowing (66.67%) and lens subluxation (73.33%) are the most characteristic findings in patients with AM with anatomical abnormalities of megalocornea and a deep anterior chamber, although corneal biometric manifestations of AM included flatter cornea and lower total corneal astigmatism. The knowledge of ocular manifestations of AM is important for diagnosis and preparation for the operation in advance to avoid intraoperative and postoperative complications. Significant differences were found in the anterior chamber and WTW values between the Pentacam HR and IOLMaster 700. Thus, we suggest that various examinations should be carefully considered before determining an AM diagnosis.

BackgroundMicrospherophakia (MSP) is a rare ocular condition, the lens surgery of which is complicated by both insufficient zonules and undersized capsule.MethodsThis study included MSP eyes managed with phacoemulsification combined with supra-capsular and scleral-fixated intraocular lens implantation (SCSF-IOL) and made the comparison with those treated by transscleral-fixated modified capsular tension ring and in-the-bag intraocular lens implantation (MCTR-IOL).ResultsA total of 20 MSP patients underwent SCSF-IOL, and 17 patients received MCTR-IOL. The postoperative best corrected visual acuity was significantly improved in both groups (P < 0.001), but no difference was found between the groups (P = 0.326). The IOL tilt was also comparable (P = 0.216). Prophylactic Nd:YAG laser posterior capsulotomy was performed 1 week to 1 month after the SCSF-IOL procedure. In the SCSF-IOL group, two eyes (10.00%) needed repeated laser treatment and one eye (5.00%) had a decentered capsule opening. Posterior capsule opacification was the most common complication (6, 35.29%) in the MCTR group. No IOL dislocation, secondary glaucoma, or retinal detachment was observed during follow-up.ConclusionsSCSF-IOL is a viable option for managing MSP and is comparable with the MCTR-IOL. Nd:YAG laser posterior capsulotomy was necessary to prevent residual capsule complications after the SCSF-IOL procedure.

Objective To observe the association between exposure to midazolam within 24 hours prior to delirium assessment and the risk of delirium. Methods We performed a systematic cohort study with two sets of cohorts to estimate the relative risks of outcomes among patients administered midazolam within 24 hours prior to delirium assessment. Propensity score matching was performed to generate a balanced 1:1 matched cohort and identify potential prognostic factors. The outcomes included the odds of delirium, mortality, length of intensive care unit stay, length of hospitalization, and odds of being discharged home. Results A total of 78,364 patients were included in this study, of whom 22,159 (28.28%) had positive records. Propensity matching successfully balanced covariates for 9348 patients (4674 per group). Compared with no administration of midazolam, midazolam administration was associated with a significantly higher risk of delirium, higher mortality, and a longer intensive care unit stay. Patients treated with midazolam were relatively less likely to be discharged home. There was no significant difference in hospitalization duration. Conclusions Midazolam may be an independent risk factor for delirium in critically ill patients.

Yunnan, located in southwestern China, harbors more than 19,000 higher plants, which represents the highest plant diversity in the country. However, plant diversity in Yunnan faces enormous threats today, including habitat destruction and fragmentation, environmental pollution, and over-exploitation of natural resources. Despite recent efforts to protect biodiversity, there are still thousands of threatened species, some of which have become extinct. We analyzed available data to gain a greater understanding of plant diversity and the status of plant conservation in Yunnan. We found that southern, southeastern, and northwestern Yunnan are hotspots of total species, endemic species, specimens, new species and threatened species, whereas southeastern Yunnan is a hotspot for plant species with extremely small populations. Moreover, we found that there are still conservation gaps and poorly protected areas in central, eastern, and northeastern Yunnan. We conclude that conservation of plant diversity in Yunnan requires modern field investigation, systematic research, the development of comprehensive databases, and government support. We recommend that conservationists pay more attention to building and improving functional protection systems and popularizing science.

Abstract Background Cold stress inhibits normal physiological metabolism in plants, thereby seriously affecting plant development. Meanwhile, plants also actively adjust their metabolism and development to adapt to changing environments. Several cold tolerance regulators have been found to participate in the regulation of plant development. Previously, we reported that BYPASS1-LIKE (B1L), a DUF793 family protein, participates in the regulation of cold tolerance, at least partly through stabilizing C-REPEAT BINDING FACTORS (CBFs). In this study, we found that B1L interacts with TRANSTHYRETIN-LIKE (TTL) protein, which is involved in brassinosteroid (BR)-mediated plant growth and catalyses the synthesis of S-allantoin, and both proteins participate in modulating plant growth and cold tolerance. Results The results obtained with yeast two hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that B1L directly interacted with TTL. Similar to the ttl-1 and ttl-2 mutants, the b1l mutant displayed a longer hypocotyl and greater fresh weight than wild type, whereas B1L-overexpressing lines exhibited a shorter hypocotyl and reduced fresh weight. Moreover, ttl-1 displayed freezing tolerance to cold treatment compared with WT, whereas the b1l mutant and TTL-overexpressing lines were freezing-sensitive. The b1l ttl double mutant had a developmental phenotype and freezing tolerance that were highly similar to those of ttl-1 compared to b1l, indicating that TTL is important for B1L function. Although low concentrations of brassinolide (0.1 or 1 nM) displayed similarly promoted hypocotyl elongation of WT and b1l under normal temperature, it showed less effect to the hypocotyl elongation of b1l than to that of WT under cold conditions. In addition, the b1l mutant also contained less amount of allantoin than Col-0. Conclusion Our results indicate that B1L and TTL co-regulate development and cold tolerance in Arabidopsis, and BR and allantoin may participate in these processes through B1L and TTL.

Covalent adaptable networks (CANs) combine the uniqueness of thermoplastics and thermosets to allow for reprocessability while being covalently crosslinked. However, it is highly desirable but rarely achieved for CANs to simultaneously demonstrate reversibility and mechanical robustness. Herein, we report a feasible strategy to develop a novel epoxy vitrimer (EV) composed of adaptable phosphate networks (APNs), by which the EVs exhibit promising mechanical properties (tensile strength of 62.5 ~ 87.8 MPa and tensile modulus of 1360.1 ~ 2975.3 MPa) under ambient conditions. At elevated temperatures, the topology rearrangement occurs relied on phosphate transesterification, which contributes to the shape memory performance, self-healing, reprocessing, and welding behaviors. Moreover, the incorporation of APNs allows for improvements in anti-ignition and also the inhibition of both heat release and smoke generation to avoid empyrosis, asphyxiation, and toxication during burning, showing expected intrinsic fire safety. Thermal, mechanical properties, and flame retardancy of the reprocessed EVs after hot pressing are very close to those of the original EVs, which is attributed to the sufficient reversibility of APNs. Accordingly, combining the aforementioned features, EVs are manufactured as flame-triggered switches for fire alarms, which symbolizes the innovative development of high-performance covalent adaptable polymeric materials.

The Fermi Large Area Telescope (LAT) has detected 6659 γ -ray sources in the incremental version (4FGL-DR3, for Data Release 3) of the fourth Fermi-LAT catalog of γ -ray sources and 3743 of them are blazars, including 1517 blazar candidates of uncertain type (BCUs). Blazars are generally classified by properties of emission lines into BL Lac objects and flat spectrum radio quasars (FSRQs). However, BCUs are difficult to classify because of the lack of spectrum. In this work we apply five different machine-learning algorithms (K-nearest neighbors, logistic regression, support vector machine, random forest, CatBoost) to evaluate the classification of 1517 BCUs based on the observational data of 4FGL-DR3. The results indicate that the use of recursive feature elimination cross-validation can effectively improve the accuracy of models and reduce computation time. We use our models to predict the BCUs from 4FGL-DR3 and the results of the overlapping of the five models are as follows: 811 BL Lac objects, 397 FSRQs, and 309 BCUs.

Exceptional alpine plant diversity exists in the Hengduan Mountains. Here, through genome assembly and population genomics studies, the authors find notable intraspecific divergence among Cushion willow populations isolated by the sky island-like habitats and consider it contributes to speciation and biodiversity.

A new species of the water scavenger beetle, Laccobius (Glyptolaccobius) motuoensis sp. nov., is described from Motuo County, Xizang, China and its diagnostic characters are illustrated. Examination of this new species and re-examination of previously described species revealed that the separation of the subgenus Glyptolaccobius Gentili, 1989 and Cyclolaccobius Gentili, 1991 is artificial: both subgenera are hence combined here. Cyclolaccobius syn. nov. is synonymized with Glyptolaccobius, and the latter is shown to be diagnosed by 7-segmented antennae as a unique synapomorphy. All species treated until now under Cyclolaccobius are here transferred to Glyptolaccobius, with the only exception of L. hingstoni Orchymont, 1926, L. jumlanus Gentili, 2015 and L. zugmayeri Knisch, 1910 which are tentatively transferred to the subgenus Hydroxenus Wollaston, 1867, as their antennae bear eight antennomeres. Three species are recorded for the first time from China: L. (Microlaccobius) orientalis Knisch, 1924 from Xizang, Laccobius (M.) exilis Gentili,1974 from Xinjiang, and Laccobius (M.) sublaevis J. Sahlberg, 1900 from Xinjiang. Additional faunistic data from China are provided for the following species: L. (Microlaccobius) hammondi Gentili, 1984, Laccobius (M.) formosus Gentili, 1979, Laccobius (Hydroxenus) hingstoni d’Orchymont, 1926, Laccobius (Glyptolaccobius) yunnanensis Gentili, 2003, Laccobius (Compsolaccobius) decorus (Gyllenhal, 1827), Laccobius (Dimorpholaccobius) bipunctatus (Fabricius, 1775), Laccobius (D.) striatulus (Fabricius, 1775), Laccobius (s. str.) bedeli Sharp, 1884, L. (s. str.) binotatus d’Orchymont, 1934, Laccobius (s. str.) cinereus Motschulsky, 1860, and Laccobius (s. str.) minutus (Linnaeus, 1758).

This study describes and illustrates Chrysosplenium macrospermum Y.I.Kim & Y.D.Kim, a new plant species from Changbaishan Mt. (Baekdusan Mt.) in northeastern China. The species is most similar to Chrysosplenium valdepilosum in the series Pilosa but is readily distinguishable by short arching sterile branches, multiple (up to 3) flowering stems, and smooth surfaced seeds (without tubercles), which are ca. 30–50% larger than those of other members in the series.

Primula dongchuanensis Z.K.Wu & Yuan Huang, a new species of Primulaceae from Dongchuan of northern Yunnan, China, is described and illustrated. Both morphological and molecular evidence support P. dongchuanensis as a member of the sect. Proliferae. It is similar to P. aurantiaca W.W.Smith & Forrest, but is distinguished by having unique raceme inflorescences. Its distribution, phenology and conservation status are also provided.

Arbitrary control of photon flow is of fundamental significance in many applications of light. Here, we propose a new approach that can trap, store, and move the signal photons to arbitrary desired place, just like what optical tweezers do on micro particles. In addition, the trapped photons can also be released at a given direction. The mechanism is based on an ultrahigh- Q nanocavity formed by two dynamically-generated potential barriers in a photonic crystal (PC) waveguide. Different from the traditional fixed ultrahigh- Q nanocavities, this new-type cavity can be formed instantaneously at any moment and any position in a PC waveguide, and is completely movable while keeps ultrahigh Q factor simultaneously. These novel features make controlling the flow of light like an optical tweezer possible, and open up new opportunities for dynamic light–matter interactions and on-chip optical signal processing.

Literature suggests important roles of a high-fat diet (HFD) in tumour development, but the underlying mechanisms remain poorly understood. This study assessed the protective effect of n-3 polyunsaturated fatty acids (PUFAs) on HFD-enhanced colon tumours and the underlying mechanism. WT mice were fed a normal fat diet or HFD and Fat-1 mice were fed a HFD for 22 weeks. For weeks 1–6, all mice were intraperitoneally administered AOM weekly. HFD significantly enhanced AOM-induced colon tumorigenesis in WT mice; however, tumour incidence and multiplicity were markedly lower in Fat-1 mice. HFD-triggered tumour development involved the activation of inflammatory signalling pathways, including TNF-α/NF-κB, IL-6/STAT3, and downstream NLRP3/IL-1β pathways and upregulation of β-catenin/c-myc pathway, which is associated with cancer cell proliferation. n-3 PUFAs inhibited colon tumour development and mitigated the changes to the aforementioned inflammatory pathways and oncogenic signalling. We provide experimental evidence for the role of n-3 PUFAs as potential chemopreventive agents against colon cancer.

Abstract Background In patients with triple valve replacement developing third-degree atrioventricular block (AVB), the most appropriate approach for permanent pacemaker implantation remains questionable. Case presentation In this case presentation, we first described the approach of implantation of the cardiac resynchronization therapy pacemaker (CRT-P) via one bipolar pacing lead in middle cardiac vein (MCV) and one quadripolar pacing lead in anterior interventricular vein (AIV) in a patient developing complete AVB, who had been previously diagnosed with rheumatic valvular heart disease with triple valve replaced. After the CRT-P implantation, the two pacing leads in coronary sinus (CS) provided a dual-site ventricular pacing from the anterior septum and posterior septum, which resulted in a narrow QRS complex and an increased ventricular synchrony. During the long-term follow-up, no deterioration of heart function was documented and pacing parameters remained good. Conclusion In this patient developing complete AVB with triple valve replaced, our approach of CRT-P implantation provides an effective and reliable ventricular pacing, and is an alternative option when transvenous right ventricular pacing, transseptal left ventricular pacing and transpericardial epicardium pacing are not possible. Further prospective randomized trials are required to confirm the efficiency of our approach of dual-site ventricular pacing by CRT-P in this kind patients.

Malrotation of the midgut is generally considered as a pediatric pathology with the majority of patients presenting in childhood. The diagnosis is rare in adults, which sometimes leads to delay in diagnosis and treatment. An index of suspicion is therefore required when dealing with patients of any age group with abdominal symptoms. We present a case of a 26-year-old male who presented with left lower abdominal pain with preoperative computed tomography showing suspected left-sided appendicitis associated with midgut malrotation. The duodenum, small bowel, and cecum were abnormally located, with the presence of a thickened and inflamed appendix with fecalith images. The patient underwent an emergency laparotomy, and ruptured cecal diverticulitis with abscess formation was confirmed. We performed a cecectomy, and the patient did not have an uneventful postoperative recovery. A review of the literature is presented to highlight the rarity of midgut malrotation and the controversies surrounding its surgical management in the adult population with ruptured left-sided cecal diverticulitis.

AIM:To investigate the safety and effect of femtosecond laser-assisted cataract surgery with Cionni modified capsular tension ring(MCTR)implantation in the management of traumatic lens subluxation.METHODS: Totally 11 patients(11 eyes)with traumatic lens subluxation were divided into three groups according to the severity of lens dislocation, ranging from 90° to 120°(4 eyes), 120° to 180°(5 eyes)and 180° to 270°(2 eyes). The contact LenSx femtosecond laser cataract surgery platform was applied to create the capsulotomy, prepare nuclear fragmentation and make corneal wound creation. Anterior vitrectomy was performed in some patients during the surgery. After capsular retractors insertion and phacoemulsification, the MCTR was inserted to the capsular bag and fixed to the sclera. Finally, the IOL was implanted into the capsular bag. Postoperative visual acuity, intra- and post-operative complications, anterior capsular opening, IOL and MCTR position and intraocular pressure(IOP)were assessed.RESULTS:The duration of follow-up was 2mo. All the operations were completed successfully. Five eyes underwent cataract surgery combined with anterior vitrectomy. Four eyes had been inserted with 2-eyelet MCTR and seven eyes with 1-eyelet MCTR. The best corrected visual acuity(BCVA)after operation was better than 0.5 in 4 eyes, between 0.3 and 0.5 in 3 eyes, between 0.1 and 0.3 in 3 eyes, and less than 0.1 in 1 eye. Compared with preoperative BCVA, the difference was statistically significant(PCONCLUSION:Femtosecond laser-assisted cataract surgery can improve the success rate of capsulorhexis, and reduce the difficulty of nuclear fragmentation. Femtosecond laser-assisted cataract surgery combined with MCTR implantation is an ideal surgical method for traumatic lens subluxation.

The C-REPEAT BINDING FACTOR signaling pathway is strictly modulated by numerous factors and is essential in the cold response of plants. Here, we show that the DUF793 family gene BYPASS1-LIKE modulates freezing tolerance through the CBFs in Arabidopsis. The expression of B1L was rapidly induced under cold treatment. Comparing to wild type, B1L knockout mutants were more sensitive to freezing treatment, whereas B1L-overexpressing lines were more tolerant. The expression of CBFs and CBF target genes was significantly decreased in b1l mutant. Using yeast two-hybrid screening system, 14-3-3λ was identified as one of proteins interacting with B1L. The interaction was confirmed with bimolecular fluorescence complementation assay and co-immunoprecipitation assay. Biochemical assays revealed that b1l mutation promoted the degradation of CBF3 compared to wild type, whereas 14-3-3κλ mutant and b1l 14-3-3κλ mutant suppressed the degradation of CBF3. Consistently, 14-3-3κλ and b1l 14-3-3κλ mutants showed enhanced freezing tolerance compared to wild type. These results indicate that B1L enhances the freezing tolerance of plants, at least partly through stabilizing CBF. Our findings improve our understanding of the regulation of CBF in response to cold stress.

Background. Neurological deficits following neurosurgical procedures are inevitable; however, there are still no effective clinical treatments. Earlier reports revealed that collagen-glycosaminoglycan (CG) matrix implantation promotes angiogenesis, neurogenesis, and functional recovery following surgical brain injury (SBI). The present study was conducted to further examine the potential neuroprotective effects of collagen-glycosaminoglycan (CG) matrix implantation following neurosurgery. Methods. CG implantation was performed in the lesion cavity created by surgical trauma. The Sprague-Dawley rat model of SBI was used as established in the previous study by the author. The rats were divided into three groups as follows: (1) sham (SHAM), (2) surgery-induced lesion cavity (L), and (3) CG matrix implantation following surgery-induced lesion cavity (L+CG). Proinflammatory (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells)) and anti-inflammatory (IL-10 and granulocyte-macrophage colony-stimulating factor (GMCSF)) cytokine expression was evaluated by enzyme-linked immunosorbent assays. Microglial activation was evaluated by immunohistochemistry, and the neuroprotective effect of CG matrix implantation was evaluated by an immunohistochemical study of microglia ED-1 and IBA-1 (activated microglia) and myeloperoxidase (MPO) and by the analysis of IL-6, IL-10, TNF-α, NF-κB, and GMCSF cytokine levels. Apoptosis was also assessed using a TUNEL assay. Results. The results showed that CG matrix implantation following surgically induced lesions significantly decreased the density of ED-1, IBA-1, and MPO (activated microglia). The tissue concentration of proinflammatory cytokines, such as TNF-α, IL-6, and NF-κB was significantly decreased. Conversely, the anti-inflammatory cytokines GMCSF and IL-10 were significantly increased. Conclusions. Implantation of the CG matrix following SBI has neuroprotective effects, including the suppression of microglial activation and the production of inflammatory-related cytokines.

With the chronic ischemia persisting after acute myocardial infarction, the accompanying low-degree inflammation and subsequent fibrosis result in progression of cardiac remodeling and heart failure. Recently, Sodium Houttuyfonate (SH), a pure compound extracted from Houttuynia cordata, has been confirmed exerting anti-inflammatory and anti-fibrotic effects under diseased situations. Here, we aimed to investigate whether SH could reverse the cardiac remodeling post-myocardial infarction by alleviating cardiac inflammation and fibrosis. Left anterior descending coronary artery of adult male Sprague-Dawley rats was ligated to elicit myocardial infarction. Low and high dose of SH was administered by oral gavage for four consecutive weeks post-myocardial infarction. Long-term SH treatment decreased heart rate, heart weight/ body weight (HW/BW), and left ventricle weight/body weight (LVW/BW), reduced cardiac expression of brain natriuretic peptide (BNP), improved left ventricular heart function, and ameliorated the histopathological changes caused by myocardial infarction. Western blotting revealed the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), collagen I, and collagen III of the infarcted ventricle were reduced by SH treatment. Meanwhile, we found that SH treatment post-myocardial infarction activated AMP-activated protein kinase (AMPK) and suppressed nuclear factor-κB p65 (NF-κB p65). Furthermore, on H9C2 cells induced hypoxic injury with cobalt chloride (CoCl2), the reduction of inflammatory cytokines (IL-6, TNF-α, and TGF-β), activation of AMPK, and suppression of NF-κB p65 were also observed by SH treatment. However, transfection of H9C2 with AMPKα siRNA blunted the suppression of NF-κB p65 and inflammatory cytokines (IL-6, TNF-α, and TGF-β) by SH post-hypoxia. Taken together, these findings suggested that long-term administration of SH post-myocardial infarction reduced cardiac inflammatory and fibrotic responses, and reversed cardiac remodeling process. The underlying mechanism may be activating AMPK and suppressing NF-κB pathway.

Background: Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control. Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely, but 10%-20% of treated patients are nonresponders to radiofrequency denervation. The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN. Methods: Seven swines randomly assigned to two groups: Renal cryoablation (CR) group and control group. The control group underwent renal angiogram only. The CR group underwent renal angiogram plus bilateral renal cryoablation. Renal angiograms via femoral were performed before denervation, after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis. Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves. Results: Cryoablation did not induce severe complications at any time point. There was no significant change in diameter of renal artery. CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg. There was a slight but insignificant decrease in diastolic BP. The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation. Compared with the control group, renal tissue NE of CR group decreased by 89.85%. Conclusions: Percutaneous catheter-based cryoablation of the renal artery is safe. CR could effectively reduce NE storing in the renal cortex, and the efficiency could be maintained 28-day at least.

Neuroinflammation has been reported to be associated with Alzheimer's disease (AD) pathogenesis. Neuroinflammation is generally considered as an outcome of glial activation; however, we recently demonstrated that T helper (Th)17 cells, a subpopulation of proinflammatory CD4+ T cells, are also involved in AD pathogenesis. Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, can be immunosuppressive, but its effects on lymphocyte-mediated neuroinflammation in AD pathogenesis have not been well addressed. In the current study we administered TGF-β1 via intracerebroventricle (ICV) and intranasal (IN) routes in AD model rats to investigate its antiinflammatory and neuroprotective effects. The AD rat model was prepared by bilateral hippocampal injection of amyloid-β (Aβ)1-42. TGF-β1 was administered via ICV one hour prior to Aβ1-42 injection or via both nares seven days after Aβ1-42 injection. ICV administration of TGF-β1 before Aβ1-42 injection remarkably ameliorated Aβ1-42-induced neurodegeneration and prevented Aβ1-42-induced increases in glia-derived proinflammatory mediators (TNF-α, IL-1β and iNOS), as well as T cell-derived proinflammatory cytokines (IFN-γ, IL-2, IL-17 and IL-22), in the hypothalamus, serum or cerebrospinal fluid (CSF) in a concentration-dependent manner. TGF-β1 pretreatment also prevented Aβ1-42-induced decreases in the neurotrophic factors, IGF-1, GDNF and BDNF, and in the antiinflammatory cytokine, IL-10. Similarly, IN administration of TGF-β1 after Aβ1-42 injection reduced neurodegeneration, elevation of proinflammatory mediators and cytokines, and reduction of neurotrophic and antiinflammatory factors, in the hypothalamus, serum or CSF. These findings suggest that TGF-β1 suppresses glial and T cell-mediated neuroinflammation and thereby alleviates AD-related neurodegeneration. The effectiveness of IN administered TGF-β1 in reducing Aβ1-42 neurotoxicity suggests a possible therapeutic approach in patients with AD.