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Abstract Purpose Sleep disorders are becoming more prevalent in hospitalized patients with acute myocardial infarction (AMI). We aimed to investigate the risk factors for sleep disorders in hospitalized patients with AMI, then develop and validate a prediction nomogram for the risk of sleep disorders. Methods Clinical data were collected from patients with AMI hospitalized in our hospital from January 2020 to June 2023. All patients were divided into the training group and the validation group with a ratio of 7:3 in sequential order. The LASSO regression analysis and multivariate logistic regression analysis were used to screen potential risk factors for sleep disorders. The concordance index (C-index), calibration curves, and decision curve analysis (DCA) were plotted. Results A total of 256 hospitalized patients with AMI were enrolled. Patients were divided into the training group (180) and the validation group (76) according to a scale of 7:3. Of the 256 patients, 90 patients (35.16%) suffered from sleep disorders, and 33 patients (12.89%) needed hypnotics. The variables screened by LASSO regression included age, smoking, NYHA class, anxiety status at admission, depression status at admission, and strangeness of environment. A nomogram model was established by incorporating the risk factors selected. The C-index, calibration curve, and DCA showed good predictive performance. Conclusions We identified six clinical characteristics as predictors of sleep disorders in hospitalized patients with AMI. It helps nurses make appropriate decisions in clinical practice.

Abstract Background Climate change is expected to alter the factors that drive changes in adaptive variation. This is especially true for species with long life spans and limited dispersal capabilities. Rapid climate changes may disrupt the migration of beneficial genetic variations, making it challenging for them to keep up with changing environments. Understanding adaptive genetic variations in tree species is crucial for conservation and effective forest management. Our study used landscape genomic analyses and phenotypic traits from a thorough sampling across the entire range of Quercus longinux, an oak species native to Taiwan, to investigate the signals of adaptation within this species. Results Using ecological data, phenotypic traits, and 1,933 single-nucleotide polymorphisms (SNPs) from 205 individuals, we classified three genetic groups, which were also phenotypically and ecologically divergent. Thirty-five genes related to drought and freeze resistance displayed signatures of natural selection. The adaptive variation was driven by diverse environmental pressures such as low spring precipitation, low annual temperature, and soil grid sizes. Using linear-regression-based methods, we identified isolation by environment (IBE) as the optimal model for adaptive SNPs. Redundancy analysis (RDA) further revealed a substantial joint influence of demography, geology, and environments, suggesting a covariation between environmental gradients and colonization history. Lastly, we utilized adaptive signals to estimate the genetic offset for each individual under diverse climate change scenarios. The required genetic changes and migration distance are larger in severe climates. Our prediction also reveals potential threats to edge populations in northern and southeastern Taiwan due to escalating temperatures and precipitation reallocation. Conclusions We demonstrate the intricate influence of ecological heterogeneity on genetic and phenotypic adaptation of an oak species. The adaptation is also driven by some rarely studied environmental factors, including wind speed and soil features. Furthermore, the genetic offset analysis predicted that the edge populations of Q. longinux in lower elevations might face higher risks of local extinctions under climate change.

Abstract We study the unflavored Schur indices in the N $$ \mathcal{N} $$ = 4 super-Yang-Mills theory for the B n , C n , D n , G 2 gauge groups. We explore two methods, namely the character expansion method and the Fermi gas method, to efficiently compute the q-series expansion of the Schur indices to some high orders. Using the available data and the modular properties, we are able to fix the exact formulas for the general gauge groups up to some high ranks and discover some interesting new features. We also identify some empirical modular anomaly equations, but unlike the case of A n groups, they are quite complicated and not sufficiently useful to fix exact formulas for gauge groups of arbitrary rank.

Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, yet the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/plateletspecific knockout of PALLD in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain (DBD) and Src homology 2 (SH2) domain via Immunoglobulin domain 3 (Ig3). Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction.

Cholecystokinin (CCK) is an essential modulator for neuroplasticity in sensory and emotional domains. Here, we investigated the role of CCK in motor learning using a single pellet reaching task in mice. Mice with a knockout of Cck gene (Cck−/−) or blockade of CCK-B receptor (CCKBR) showed defective motor learning ability; the success rate of retrieving reward remained at the baseline level compared to the wildtype mice with significantly increased success rate. We observed no long-term potentiation upon high-frequency stimulation in the motor cortex of Cck−/− mice, indicating a possible association between motor learning deficiency and neuroplasticity in the motor cortex. In vivo calcium imaging demonstrated that the deficiency of CCK signaling disrupted the refinement of population neuronal activity in the motor cortex during motor skill training. Anatomical tracing revealed direct projections from CCK-expressing neurons in the rhinal cortex to the motor cortex. Inactivation of the CCK neurons in the rhinal cortex that project to the motor cortex bilaterally using chemogenetic methods significantly suppressed motor learning, and intraperitoneal application of CCK4, a tetrapeptide CCK agonist, rescued the motor learning deficits of Cck−/− mice. In summary, our results suggest that CCK, which could be provided from the rhinal cortex, may surpport motor skill learning by modulating neuroplasticity in the motor cortex.

Abstract Prostate cancer (PCa) patients with lymph node involvement (LNI) constitute a single-risk group with varied prognoses. Existing studies on this group have focused solely on those who underwent prostatectomy (RP), using statistical models to predict prognosis. This study aimed to develop an easily accessible individual survival prediction tool based on multiple machine learning (ML) algorithms to predict survival probability for PCa patients with LNI. A total of 3280 PCa patients with LNI were identified from the Surveillance, Epidemiology, and End Results (SEER) database, covering the years 2000–2019. The primary endpoint was overall survival (OS). Gradient Boosting Survival Analysis (GBSA), Random Survival Forest (RSF), and Extra Survival Trees (EST) were used to develop prognosis models, which were compared to Cox regression. Discrimination was evaluated using the time-dependent areas under the receiver operating characteristic curve (time-dependent AUC) and the concordance index (c-index). Calibration was assessed using the time-dependent Brier score (time-dependent BS) and the integrated Brier score (IBS). Moreover, the beeswarm summary plot in SHAP (SHapley Additive exPlanations) was used to display the contribution of variables to the results. The 3280 patients were randomly split into a training cohort (n = 2624) and a validation cohort (n = 656). Nine variables including age at diagnosis, race, marital status, clinical T stage, prostate-specific antigen (PSA) level at diagnosis, Gleason Score (GS), number of positive lymph nodes, radical prostatectomy (RP), and radiotherapy (RT) were used to develop models. The mean time-dependent AUC for GBSA, RSF, and EST was 0.782 (95% confidence interval [CI] 0.779–0.783), 0.779 (95% CI 0.776–0.780), and 0.781 (95% CI 0.778–0.782), respectively, which were higher than the Cox regression model of 0.770 (95% CI 0.769–0.773). Additionally, all models demonstrated almost similar calibration, with low IBS. A web-based prediction tool was developed using the best-performing GBSA, which is accessible at https://pengzihexjtu-pca-n1.streamlit.app/ . ML algorithms showed better performance compared with Cox regression and we developed a web-based tool, which may help to guide patient treatment and follow-up.

Abstract Mitochondria are essential organelles for cellular metabolism and physiology in eukaryotic cells. Human mitochondria have their own genome (mtDNA), which is maternally inherited with 37 genes, encoding 13 polypeptides for oxidative phosphorylation, and 22 tRNAs and 2 rRNAs for translation. mtDNA mutations are associated with a wide spectrum of degenerative and neuromuscular diseases. However, the pathophysiology of mitochondrial diseases, especially for threshold effect and tissue specificity, is not well understood and there is no effective treatment for these disorders. Especially, the lack of appropriate cell and animal disease models has been significant obstacles for deep elucidating the pathophysiology of maternally transmitted diseases and developing the effective therapy approach. The use of human induced pluripotent stem cells (iPSCs) derived from patients to obtain terminally differentiated specific lineages such as inner ear hair cells is a revolutionary approach to deeply understand pathogenic mechanisms and develop the therapeutic interventions of mitochondrial disorders. Here, we review the recent advances in patients-derived iPSCs as ex vivo models for mitochondrial diseases. Those patients-derived iPSCs have been differentiated into specific targeting cells such as retinal ganglion cells and eventually organoid for the disease modeling. These disease models have advanced our understanding of the pathophysiology of maternally inherited diseases and stepped toward therapeutic interventions for these diseases.

Summary: Mitochondria are dynamic organelles in cellular metabolism and physiology. Mitochondrial DNA (mtDNA) mutations are associated with a broad spectrum of clinical abnormalities. However, mechanisms underlying mtDNA mutations regulate intracellular signaling related to the mitochondrial and cellular integrity are less explored. Here, we demonstrated that mt-tRNAMet 4435A>G mutation-induced nucleotide modification deficiency dysregulated the expression of nuclear genes involved in cytosolic proteins involved in oxidative phosphorylation system (OXPHOS) and impaired the assemble and integrity of OXPHOS complexes. These dysfunctions caused mitochondrial dynamic imbalance, thereby increasing fission and decreasing fusion. Excessive fission impaired the process of autophagy including initiation phase, formation, and maturation of autophagosome. Strikingly, the m.4435A>G mutation upregulated the PARKIN dependent mitophagy pathways but downregulated the ubiquitination-independent mitophagy. These alterations promoted intrinsic apoptotic process for the removal of damaged cells. Our findings provide new insights into mechanism underlying deficient tRNA posttranscription modification regulated intracellular signaling related to the mitochondrial and cellular integrity.

Abstract Background Leber’s hereditary optic neuropathy (LHON) is a maternally inherited eye disease due to mutations in mitochondrial DNA. However, there is no effective treatment for this disease. LHON-linked ND6 14484T > C (p.M64V) mutation caused complex I deficiency, diminished ATP production, increased production of reactive oxygen species (ROS), elevated apoptosis, and impaired mitophagy. Here, we investigated if the allotopic expression of human mitochondrial ND6 transgene corrected the mitochondrial dysfunctions due to LHON-associated m.14484T > C mutation. Methods Nucleus-versions of ND6 was generated by changing 6 non-universal codons with universal codons and added to mitochondrial targeting sequence of COX8. Stable transfectants were generated by transferring human ND6 cDNA expressed in a pCDH-puro vector into mutant cybrids carrying the m.14484T > C mutation and control cybrids. The effect of allotopic expression of ND6 on oxidative phosphorylation (OXPHOS) was evaluated using Blue Native gel electrophoresis and extracellular flux analyzer. Assessment of ROS production in cell lines was performed by flow cytometry with MitoSOX Red reagent. Analyses for apoptosis and mitophagy were undertaken via flow cytometry, TUNEL and immunofluorescence assays. Results The transfer of human ND6 into the cybrids carrying the m.14484T > C mutation raised the levels of ND6, ND1 and ND4L but did not change the levels of other mitochondrial proteins. The overexpression of ND6 led to 20~23% increases in the assembly and activity of complex I, and ~ 53% and ~ 33% increases in the levels of mitochondrial ATP and ΔΨm in the mutant cybrids bearing m.14484T > C mutation. Furthermore, mutant cybrids with overexpression of ND6 exhibited marked reductions in the levels of mitochondrial ROS. Strikingly, ND6 overexpression markedly inhibited the apoptosis process and restored impaired mitophagy in the cells carrying m.14484T > C mutation. However, overexpression of ND6 did not affect the ND6 level and mitochondrial functions in the wild-type cybrids, indicating that this ND6 level appeared to be the maximum threshold level to maintain the normal cell function. Conclusion We demonstrated that allotopic expression of nucleus-versions of ND6 restored complex I, apoptosis and mitophagy deficiencies caused by the m.14484T > C mutation. The restoration of m.14484T > C mutation-induced mitochondrial dysfunctions by overexpression of ND6 is a step toward therapeutic interventions for LHON and mitochondrial diseases.

The pyrolysis performances and reaction kinetics of pine needles (PN) were investigated by integrating thermogravimetric analysis, Fourier transform infrared spectroscopy, and pyrolysis-gas chromatography/mass spectrometry. The average activation energy of PN was estimated to be 183.2 kJ/mol by Kissinger Akahira Sunose (KAS) and 183.8 kJ/mol by Flynn Wall Ozawa (FWO), respectively at heating rates of 10, 20, and 40 °C/min. The pyrolysis of PN was found to be more efficient at the lower heating rates, while increased heating rates promoted the reaction. Using the King-Kai (K-K) method, the activation energies of hemicellulose, cellulose, and lignin were calculated to be 156, 165, and 172 kJ/mol, respectively. The descending order of evolving gases and functional groups from PN was found to be CO2, C=C, C=O, H2O, CH4, and CO. The main pyrolytic by-products identified were hydrocarbons, phenols, alcohols, ketones, and aldehydes. The determination of kinetic parameters provides fundamental information for predicting the rates at which chemical reactions occur. This study demonstrates the potential of PN as a suitable source for bioenergy.

The pyrolysis performances and reaction kinetics of pine needles (PN) were investigated by integrating thermogravimetric analysis, Fourier transform infrared spectroscopy, and pyrolysis-gas chromatography/mass spectrometry. The average activation energy of PN was estimated to be 183.2 kJ/mol by Kissinger Akahira Sunose (KAS) and 183.8 kJ/mol by Flynn Wall Ozawa (FWO), respectively at heating rates of 10, 20, and 40 °C/min. The pyrolysis of PN was found to be more efficient at the lower heating rates, while increased heating rates promoted the reaction. Using the King-Kai (K-K) method, the activation energies of hemicellulose, cellulose, and lignin were calculated to be 156, 165, and 172 kJ/mol, respectively. The descending order of evolving gases and functional groups from PN was found to be CO2, C=C, C=O, H2O, CH4, and CO. The main pyrolytic by-products identified were hydrocarbons, phenols, alcohols, ketones, and aldehydes. The determination of kinetic parameters provides fundamental information for predicting the rates at which chemical reactions occur. This study demonstrates the potential of PN as a suitable source for bioenergy.

Aspidistra Ker Gawl. is one of the the most diverse and fastest-growing genera of angiosperm. Most Aspidistra species have been discovered in a limited area or a single site through morphological comparison. Because of the lack of population studies, morphological variation within species and the boundaries of some species remain unclear. In recent years, combining genetic and morphological markers has become a powerful approach for species delimitation. In this study, we performed population sampling and integrated morphometrics and microsatellite genetic diversity analyses to determine the species diversity of Aspidistra in Taiwan. We identified three species, namely Aspidistra attenuata Hayata; A. daibuensis Hayata var. daibuensis; A. mushaensis Hayata var. mushaensis; and reduced A. longiconnectiva C.T.Lu, K.C.Chuang & J.C.Wang to the variety level, and described a new variety, A. daibuensis Hayata var. longkiauensis. The description, diagnosis, distribution, and photographs of this new variety as well as a key to the known Taiwanese Aspidistra are provided.

We consider the von Neumann entropy of a thermal mixed state in quantum systems derived from mirror curves, where the kinetic terms are exponential functions of the momentum operators. Using the mathematical results on the asymptotics of the energy eigenvalues, we compute the asymptotic entropy in high temperature limit and compare with that of the conventional models. We discuss the connections with some folklores in quantum gravity, particularly on the finiteness of entropy.

Abstract A cryptic lineage is a genetically diverged but morphologically unrecognized variant of a known species. Clarifying cryptic lineage evolution is essential for quantifying species diversity. In sympatric cryptic lineage divergence compared with allopatric divergence, the forces of divergent selection and mating patterns override geographical isolation. Introgression, by supplying preadapted or neutral standing genetic variations, can promote sympatric cryptic lineage divergence via selection. However, most studies concentrated on extant species introgression, ignoring the genetic legacy of introgression from extinct or unsampled lineages (“ghost introgression”). Cycads are an ideal plant for studying the influence of ghost introgression because of their common interspecific gene flow and past high extinction rate. Here, we utilized reference‐based ddRADseq to clarify the role of ghost introgression in the evolution of a previously identified sympatric cryptic lineage in Cycas revoluta. After re‐evaluating the evolutionary independency of cryptic lineages, the group‐wise diverged single‐nucleotide polymorphisms among sympatric and allopatric lineages were compared and functionally annotated. Next, we employed an approximate Bayesian computation method for hypothesis testing to clarify the cryptic lineage evolution and ghost introgression effect. SNPs with the genomic signatures of ghost introgression were further annotated. Our results reconfirmed the evolutionary independency of cryptic lineage among C. revoluta and demonstrated that ghost introgression to the noncryptic lineage facilitated their divergence. Gene function related to heat stress and disease resistance implied ecological adaptation of the main extant populations of C. revoluta.

IntroductionThe pathogenic gene CDH23 plays a pivotal role in tip links, which is indispensable for mechanoelectrical transduction in the hair cells. However, the underlying molecular mechanism and signal regulatory networks that influence deafness is still largely unknown.MethodsIn this study, a congenital deafness family, whole exome sequencing revealed a new mutation in the pathogenic gene CDH23, subsequently; the mutation has been validated using Sanger sequencing method. Then CRISPR/Cas9 technology was employed to knockout zebrafish cdh23 gene. Startle response experiment was used to compare with wide-type, the response to sound stimulation between wide-type and cdh23−/−. To further illustrate the molecular mechanisms underlying congenital deafness, comparative transcriptomic profiling and multiple bioinformatics analyses were performed.ResultsThe YO-PRO-1 assay result showed that in cdh23 deficient embryos, the YO-PRO-1 signal in inner ear and lateral line neuromast hair cells were completely lost. Startle response experiment showed that compared with wide-type, the response to sound stimulation decreased significantly in cdh23 mutant larvae. Comparative transcriptomic showed that the candidate genes such as atp1b2b and myof could affect hearing by regulating ATP production and purine metabolism in a synergetic way with cdh23. RT-qPCR results further confirmed the transcriptomics results. Further compensatory experiment showed that ATP treated cdh23−/− embryos can partially recover the mutant phenotype.ConclusionIn conclusion, our study may shed light on deciphering the principal mechanism and provide a potential therapeutic method for congenital hearing loss under the condition of CDH23 mutation.

Objective To construct and internally validate a nomogram that predicts the likelihood of postoperative delirium in a cohort of elderly individuals undergoing hip arthroplasty.Methods Data for a total of 681 elderly patients underwent hip arthroplasty were retrospectively collected and divided into a model (n = 477) and a validation cohort (n = 204) according to the principle of 7:3 distribution temporally. The assessment of postoperative cognitive function was conducted through the utilization of The Confusion Assessment Method (CAM). The nomogram model for postoperative cognitive impairments was established by a combination of Lasso regression and logistic regression. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance.Results The nomogram utilized various predictors, including age, body mass index (BMI), education, preoperative Barthel Index, preoperative hemoglobin level, history of diabetes, and history of cerebrovascular disease, to forecast the likelihood of postoperative delirium in patients. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.836 (95% CI: 0.797–0.875) for the training set and 0.817 (95% CI: 0.755–0.880) for the validation set. The calibration curves for both sets indicated a good agreement between the nomogram’s predictions and the actual probabilities.Conclusion The use of this novel nomogram can help clinicians predict the likelihood of delirium after hip arthroplasty in elderly patients and help prevent and manage it in advance.

This study identifies the evolutionarily conserved Exportin 4 as an essential regulator in the nuclear export of circRNAs. Defective circRNA export results in R-loop formation and DNA damage in cells, as well as testis and neurological defects in mice.

Abstract We propose a novel modular anomaly equation for the unflavored Schur index in the N $$ \mathcal{N} $$ = 4 SU(N) super-Yang-Mills theory. The vanishing conditions overdetermine the modular ambiguity ansatz from the equation, thus together they are sufficient to recursively compute the exact Schur indices for all SU(N) gauge groups. Using the representations as MacMahon’s generalized sum-of-divisors functions and Jacobi forms, we then prove our proposal as well as elucidate a general formula conjectured by Pan and Peelaers.

Abstract We propose the refined topological string correspondence to the expectation values of half-BPS Wilson loop operators in 5d N $$ \mathcal{N} $$ = 1 gauge theory partition function on the Omega-deformed background ℝ ϵ 1 , 2 4 $$ {\mathbb{R}}_{\upepsilon_{1,2}}^4 $$ × S 1. We provide the refined topological vertex method and the refined holomorphic anomaly equation method in the topological string theory, from which we have exact computations on the 5d Wilson loops partition functions in both A- and B-models. Finally, with the exact results we have in B-model, we recover the quantum periods of local ℙ1 × ℙ1 model and local ℙ2 model in the study of quantum geometry and we further give a refined generalization of A-period.

Abstract. To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women's and Children's Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.

The ADP/ATP carrier (AAC) is crucial for mitochondrial functions by importing ADP and exporting ATP across the inner mitochondrial membrane. However, the mechanism of highly specific ADP recognition and transport by AAC remains largely elusive. In this work, spontaneous ADP binding process to the ground c-state AAC was investigated through rigorous molecular dynamics simulations of over 31 microseconds in total. With improved simulation strategy, we have successfully identified a highly specific ADP binding site in the upper region of the cavity, and this site exhibits selectivity for ADP over ATP based on free-energy calculations. Sequence analyses on adenine nucleotide transporters also suggest that this subgroup uses the upper region of the cavity, rather than the previously proposed central binding site located at the bottom of the cavity to discriminate their substrates. Identification of the new site unveils the unusually high substrate specificity of AAC and explains the dependence of transport on the flexibility between anti and syn glycosidic conformers of ADP. Moreover, this new site together with the central site supports early biochemical findings. In light of these early findings, our simulations described a multi-step model in which the carrier uses different sites for substrate attraction, recognition and conformational transition. These results provide new insights into the transport mechanism of AAC and other adenine nucleotide transporters.

Insulator defect detection is of great significance to compromise the stability of the power transmission line. The state-of-the-art object detection network, YOLOv5, has been widely used in insulator and defect detection. However, the YOLOv5 network has limitations such as poor detection rate and high computational loads in detecting small insulator defects. To solve these problems, we proposed a light-weight network for insulator and defect detection. In this network, we introduced the Ghost module into the YOLOv5 backbone and neck to reduce the parameters and model size to enhance the performance of unmanned aerial vehicles (UAVs). Besides, we added small object detection anchors and layers for small defect detection. In addition, we optimized the backbone of YOLOv5 by applying convolutional block attention modules (CBAM) to focus on critical information for insulator and defect detection and suppress uncritical information. The experiment result shows the mean average precision (mAP) is set to 0.5, and the mAP is set from 0.5 to 0.95 of our model and can reach 99.4% and 91.7%; the parameters and model size were reduced to 3,807,372 and 8.79 M, which can be easily deployed to embedded devices such as UAVs. Moreover, the speed of detection can reach 10.9 ms/image, which can meet the real-time detection requirement.

Objectives: To develop a population pharmacokinetic (PopPK) model describing unbound teicoplanin concentrations in Chinese adult patients and perform Monte Carlo simulations to optimize the dosing regimens.Methods: The raw data for PopPK analysis in this study were collected from Chinese adult patients. A PopPK model of unbound teicoplanin was developed and Monte Carlo simulations were used to optimize the dosing regimens. The trough concentrations of unbound teicoplanin were targeted at 0.75 mg/L and 1.13 mg/L for most infection induced by Gram-positive bacteria and endocarditis or severe infections, respectively.Results: A total of 103 teicoplanin unbound concentrations were collected from 72 Chinese adult patients. A one-compartment pharmacokinetic model with first-order elimination was established. The typical values of clearance and the volume of distribution were 11.7 L/h and 811 L, respectively. The clearance and volume of distribution of unbound teicoplanin were positively correlated with estimated glomerular filtration rate (eGFR) and serum albumin concentrations, respectively. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and the dosing regimen need optimize based on eGFR and serum albumin concentrations. The high eGFR and serum albumin concentration were associated with reduced probability of achieving target unbound trough concentrations.Conclusion: We successfully characterized the pharmacokinetics of unbound teicoplanin in Chinese adult patients. Importantly, we further highlight the importance of guiding dosing through unbound drugs. To achieve safe and effective treatment, the dosing regimens need to be adjusted according to eGFR and serum albumin concentrations.

Abstract Recently, we proposed a novel entry of the pp-wave holographic dictionary, which equated the Berenstein-Maldacena-Nastase (BMN) two-point functions in free N $$ \mathcal{N} $$ = 4 super-Yang-Mills theory with the norm squares of the quantum unitary transition amplitudes between the corresponding tensionless strings in the infinite curvature limit, for the cases with no more than three string modes in different transverse directions. A seemingly highly non-trivial conjectural consequence, particularly in the case of three string modes, is the non-negativity of the BMN two-point functions at any higher genus for any mode numbers. In this paper, we further perform the detailed calculations of the BMN two-point functions with three string modes at genus two, and explicitly verify that they are always non-negative through mostly extensive numerical tests.

Abstract Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

Abstract Recently, Okuyama and Sakai proposed a novel holomorphic anomaly equation for the partition function of 2d Yang-Mills theory on a torus, based on an anholomorphic deformation of the propagator in the bosonic formulation. Using the boson-fermion correspondence, we derive the formula for the deformed partition function in fermionic description and give a proof of the holomorphic anomaly equation.

Range expansion requires peripheral populations to shift adaptive optima to breach range boundaries. Opportunities for range expansion can be assessed by investigating the associations of core-periphery environmental and genetic differences. This study investigates differences in the core-periphery adaptation of Ammopiptanthus mongolicus, a broad-leaved evergreen shrub species in a relatively homogeneous temperate Asian desert environment, to explore the environmental factors that limit the expansion of desert plants. Temperate deserts are characterized by severe drought, a large diurnal temperature range, and seasonality. Long-standing adaptation to the harsh desert environment may confine the genetic diversity of A. mongolicus, despite its distribution over a wide range of longitude, latitude, and altitude. Since range edges defined by climate niches may have different genetic responses to environmental extremes, we compared genome-wide polymorphisms between nine environmental core populations and ten fragmented peripheral populations to determine the “adaptive peripheral” populations. At least four adaptive peripheral populations had similar genetic-environmental association patterns. High elevations, summer drought, and winter cold were the three main determinants of converging these four adaptive peripheral populations. Elevation mainly caused similar local climates among different geographic regions. Altitudinal adaptation resulting from integrated environmental-genetic responses was a breakthrough in breaching niche boundaries. These peripheral populations are also located in relatively humid and warmer environments. Relaxation of the drought and cold constraints facilitated the genetic divergence of these peripheral populations from the core population’s adaptive legacy. We conclude that pleiotropic selection synchronized adaptative divergence to cold and drought vs. warm and humid environments between the core and peripheral populations. Such parallel adaptation of peripheral populations relies on selection under a background of abundant new variants derived from the core population’s standing genetic variation, i.e., integration of genetic surfing and local adaptation.

The “Internet Plus” education model, enabled by the internet, is a type of “Distance learning” education models. To explore the application of “Internet Plus” education in teaching physiological experimentation at Guilin Medical University, undergraduate clinical medicine students from the 2011 to 2013 classes were used as the historical control group for teaching an experimentation class using the traditional teaching model: “teacher-teaching + student-operation.” Undergraduate clinical medicine students from the 2014 to 2018 classes were used as the teaching reform group and were taught using an “Internet Plus” educational model: “microlectures-previewing + test + feedback + student-operation.” The experimentation operating examination results for the two groups of students were analyzed, questionnaire surveys were administered to students in the experimental group and the relevant teachers, and the survey results were counted. The experimentation operating examination results were significantly higher for the students in the teaching reform group (89.3 points) than for the control group students (84.4 points). The excellent rate was higher (69.8% for the reform group and 54.5% for the control group), whereas the failure rate was lower (1.9% for the teaching reform group and 4.3% for the control group). Additionally,90.1% of the students identified with this reform method, and more than 90% believed that the method improved their interest and confidence in surgical operations during pharmacological and pathophysiological experimentation classes in subsequent courses. All teachers in the physiological experimentation course identified with this teaching method, and 81.8% of the teachers of relevant disciplines in a later stage believed that this learning method was more conducive than traditional teaching to cultivating student interest in learning, proactivity, and other factors. Application of an “Internet Plus” educational model for physiological experimentation teaching can help cultivate hands-on operating abilities and improve the learning interest of students.

Inherited kidney diseases are the fifth most common cause of end-stage renal disease (ESRD). Mitochondrial dysfunction plays a vital role in the progression of inherited kidney diseases, while mitochondrial-transfer RNA (mt-tRNA) variants and their pathogenic contributions to kidney disease remain largely unclear. In this study, we identified the pathogenic mt-tRNAPhe 616T>C mutation in 3 families and documented that m.616T>C showed a high pathogenic threshold, with both heteroplasmy and homoplasmy leading to isolated chronic kidney disease and hyperuricemia without hematuria, proteinuria, or renal cyst formation. Moreover, 1 proband with homoplamic m.616T>C presented ESRD as a child. No symptoms of nervous system evolvement were observed in these families. Lymphoblast cells bearing m.616T>C exhibited swollen mitochondria, underwent active mitophagy, and showed respiratory deficiency, leading to reduced mitochondrial ATP production, diminished membrane potential, and overproduction of mitochondrial ROS. Pathogenic m.616T>C abolished a highly conserved base pair (A31-U39) in the anticodon stem-loop which altered the structure of mt-tRNAPhe, as confirmed by a decreased melting temperature and slower electrophoretic mobility of the mutant tRNA. Furthermore, the unstable structure of mt-tRNAPhe contributed to a shortage of steady-state mt-tRNAPhe and enhanced aminoacylation efficiency, which resulted in impaired mitochondrial RNA translation and a significant decrease in mtDNA–encoded polypeptides. Collectively, these findings provide potentially new insights into the pathogenesis underlying inherited kidney disease caused by mitochondrial variants.

Abstract Purpose The present study aimed to explore the clinical characteristics of heparin-induced thrombocytopenia (HIT) after surgery for acute type A aortic dissection and perform a relevant prognostic analysis. Methods After continuous observation and analysis of 204 patients who underwent acute type A aortic dissection, we found that blood platelets decreased significantly after surgery and that these patients can be suspected to suffer HIT based on relevant 4Ts scores. For these suspected HIT patients, a latex particle-enhanced immunoturbidimetric assay was conducted to detect heparin-induced antibodies. Perioperative clinical data of patients in HIT and non-HIT groups were recorded as were blood platelet counts, HIT antibody test results, 4Ts scores, thromboembolic complications, clinical prognosis and outcomes. Results In the present study, 38 suspected HIT patients, 16 HIT patients and 188 non-HIT patients were selected in the clinical setting. Among them, HIT patients were found to have prolonged cardiopulmonary bypass time (223 min on average vs. 164 min) and delayed aortic cross-clamp time (128 min on average vs. 107 min), and these differences between HIT patients and non-HIT patients were significant (P 0.05). The transfusions of blood platelets in the HIT group and non-HIT group were 18.7 ± 5.0u and 15.6 ± 7.34 u, respectively. In the HIT group, the mechanic ventilation time and the length of ICU stay were longer comparing the non-HIT group(P 0.05). The incidence of continuous renal replacement therapy in HIT group was higher than the non-HIT group (P 0.05). However, the HIT antibody titer in the HIT group was significantly higher than that in the Suspected HIT group (2.7 ± 0.8 U/mL vs. 0.3 ± 0.2 U/mL) (P

Abstract In the type IIB maximally supersymmetric pp-wave background, stringy excited modes are described by BMN (Berenstein-Madalcena-Nastase) operators in the dual N $$ \mathcal{N} $$ = 4 super-Yang-Mills theory. In this paper, we continue the studies of higher genus free BMN correlators with more stringy modes, mostly focusing on the case of genus one and four stringy modes in different transverse directions. Surprisingly, we find that the non-negativity of torus two-point functions, which is a consequence of a previously proposed probability interpretation and has been verified in the cases with two and three stringy modes, is no longer true for the case of four or more stringy modes. Nevertheless, the factorization formula, which is also a proposed holographic dictionary relating the torus two-point function to a string diagram calculation, is still valid. We also check the correspondence of planar three-point functions with Green-Schwarz string vertex with many string modes. We discuss some issues in the case of multiple stringy modes in the same transverse direction. Our calculations provide some new perspectives on pp-wave holography.

Abstract We make a proposal for calculating refined Gopakumar-Vafa numbers (GVN) on elliptically fibered Calabi-Yau 3-folds based on refined holomorphic anomaly equations. The key examples are smooth elliptic fibrations over (almost) Fano surfaces. We include a detailed review of existing mathematical methods towards defining and calculating the (unrefined) Gopakumar-Vafa invariants (GVI) and the GVNs on compact Calabi-Yau 3-folds using moduli of stable sheaves, in a language that should be accessible to physicists. In particular, we discuss the dependence of the GVNs on the complex structure moduli and on the choice of an orientation. We calculate the GVNs in many instances and compare the B-model predictions with the geometric calculations. We also derive the modular anomaly equations from the holomorphic anomaly equations by analyzing the quasi-modular properties of the propagators. We speculate about the physical relevance of the mathematical choices that can be made for the orientation.

Abstract. Objective:. This study was performed to evaluate the clinical and epidemiological characteristics of inpatients with malignant skin tumors in western Inner Mongolia during the past 10 years. Methods:. We collected the clinical data of inpatients with histopathologically diagnosed malignant skin tumors admitted to the Affiliated Hospital of Inner Mongolia Medical University from June 2008 to December 2018. Morbidity was compared using the Chi-square test. Results:. In total, 340 inpatients with malignant skin tumors were evaluated, including 163 (47.94%) patients with basal cell carcinoma, 134 (39.41%) with squamous cell carcinoma, 5 (1.47%) with malignant melanoma, 21 (6.18%) with Bowen disease, and 6 (1.76%) with Paget's disease. Four (1.18%) patients had metastatic skin cancer and seven (2.06%) had other malignant skin tumors. The patients comprised 132 (38.8%) men and 208 (61.1%) women, and there were no statistically significant sex-related differences among the skin malignancies (x2 = 5.006, P > 0.05). Among the 340 patients, 314 (92.4%) were of Han nationality and 26 (7.6%) were of ethnic minorities. Statistically significant differences were found in the various types of malignant skin tumors between the Han and minority groups (x2 = 19.446, P

The divergence process of incipient species is fascinating but elusive by incomplete lineage sorting or gene flow. Species delimitation is also challenging among those morphologically similar allopatric species, especially when lacking comprehensive data. Cycas sect. Asiorientales, comprised of C. taitungensis and C. revoluta in the Ryukyu Archipelago and Taiwan, diverged recently with continuous gene flow, resulting in a reciprocal paraphyletic relationship. Their previous evolutionary inferences are questioned from few genetic markers, incomplete sampling, and incomprehensive morphological comparison by a long-term taxonomic misconception. By whole range sampling, this study tests the geographic mode of speciation in the two species of Asiorientales by approximate Bayesian computation (ABC) using genome-wide single nucleotide polymorphisms (SNPs). The individual tree was reconstructed to delimit the species and track the gene-flow trajectory. With the comparison of diagnostic morphological traits and genetic data, the allopatric speciation was rejected. Alternatively, continuous but spatially heterogeneous gene flow driven by transoceanic vegetative dispersal and pollen flow with contrasting population sizes blurred their species boundary. On the basis of morphological, genetic, and evolutionary evidence, we synonymized these two Cycas species. This study highlights not only the importance of the Kuroshio Current to species evolution but also the disadvantage of using species with geographically structured genealogies as conservation units.

Abstract We continue the study of a novel relation between quantum periods and TBA(Thermodynamic Bethe Ansatz)-like difference equations, generalize previous works to a large class of Calabi-Yau geometries described by three-term quantum operators. We give two methods to derive the TBA-like equations. One method uses only elementary functions while the other method uses Faddeev’s quantum dilogarithm function. The two approaches provide different realizations of TBA-like equations which are nevertheless related to the same quantum period.

Objective: To identify the sociodemographic characteristics, motivations, and semen parameters of sperm donors in Shanghai, China. Methods: The participants were sperm donors associated with the Human Sperm Bank of Fudan University in Shanghai, China. Among the 334 sperm donors that applied for participation, 329 completed the survey process. The responses obtained in the questionnaire and face-to-face interviews were used to investigate the donor motivations and characteristics, and the semen quality was examined to identify the sperm parameter. Results: In terms of the sociodemographic characteristics, an altruistic donor in this study was aged between 26 and 30 years, was single, did not have a child, had a college or undergraduate education level, was of the Han ethnicity, and worked full time. The strongest motivation highlighted by sperm donors was a donation for altruistic (26.4%, n = 87) reasons. The second-highest rated motivation was curiosity (20.7%, n = 68), followed by a desire to procreate (17.9%, n = 59). “Complimentary body checks” (14.3%, n = 47) and “financial incentives” (14.7%, n = 47) were regarded as less important. The average semen parameters of the 329 donors were as follows: the semen volume was 3.39 ± 1.21 mL, the semen concentration was 82.75 × 106/mL, the progressive motility rate (PR%) was 63.77% ± 3.13%, the total motility rate was 66.26%, the total progressive motile count was 158.31% ± 54.43 × 106/mL, and the round cell concentration was 0.38 ± 0.51 × 106/mL. The PR% of the procreation motivation group was significantly higher than that of the other motivation groups (P < 0.05). Conclusions: Sperm donors in Shanghai, China, are altruistic about their donation, although curiosity is also a key motivator. In addition, the decisions of donors are culturally influenced, and the motivation to procreate may influence the PR%.

Using genetic code expansion, Zhao, Shi et al. generate light-sensitive tyrosine analogues to obtain insights into the activation of the NGF receptor, TrkA. They identify light-sensitive and NGF-insensitive phosphorylation sites, validating the approach and providing insights into TrkA signaling

Abstract We study a class of quantum integrable systems derived from dimer graphs and also described by local toric Calabi-Yau geometries with higher genus mirror curves, generalizing some previous works on genus one mirror curves. We compute the spectra of the quantum systems both by standard perturbation method and by Bohr-Sommerfeld method with quantum periods as the phase volumes. In this way, we obtain some exact analytic results for the classical and quantum periods of the Calabi-Yau geometries. We also determine the differential operators of the quantum periods and compute the topological string free energy in Nekrasov-Shatashvili (NS) limit. The results agree with calculations from other methods such as the topological vertex.

ABSTRACT: The Eastern Kunlun Orogenic Belt (EKOB) has a complex geological structure and diverse magmatic activities, which are closely related to the Qaidam Basin and the Tethys tectonic evolution. There are at least 3 stages mafic-ultramafic rocks occurred in the Early Paleozoic in EKOB. The first stage is the Later-Silurian to Early Devonian, represented by the giant Xiarihamu super large magmatic Cu-Ni deposit, containing about 1.18 million metric tons (Mt) of nickel with average grades of 0.65% Ni, and its age of ore-forming pyroxene peridotite is 411 Ma; The second stage is the Early Carboniferous, represented by the large Shitoukengde magmatic Cu-Ni sulfide deposit, and its ore-forming age of the olivine websterite is 334 Ma; The third stage of mafic-ultramafic rocks occurred mainly during the Middle-Late Triassic, represented by Xiaojianshan, Lalinggaoli, and Kaimuqi complexes, and no economical ore bodies have been found in this period. The authors summarized the difference between the ore-bearing and the nonmineralized mafic-ultramafic rocks in the EKOB. The olivine of the ore-bearing complexes contains higher MgO and SiO2 content but lower FeO and CaO contents, and the clinopyroxene of ore-bearing complexes contains lower FeO and CaO contents. Crustal sulfur contamination is key to the formation of the giant Xiarihamu Ni deposit, and crustal sulfur contamination degree of the giant magmatic Ni deposit is higher than that of large Ni deposit. The above indicators could guide the exploration and evaluation of similar deposits in the EKOB.

Fagaceae species predominate a diverse range of habitats in the northern hemisphere and are critical to the ecosystem and economy. The high morphological and genetic diversity of these species serves as the foundation for adaptation to environmental stress. To comprehend the diversity, an evolutionary viewpoint is required. However, we found extensive conflicts among gene trees at the genus level, resulting in inconclusive phylogenetic inferences based on various genetic markers. Unresolved phylogeny would affect taxonomy, biogeographic inference, and ancestral state. In this study, we aimed to look deeply into the source of phylogenetic discordance in Fagaceae. We sampled 65 species from six genera (Fagus, Lithocarpus, Quercus, Castanea, Castanopsis, and Notholithocarpus) and obtained 603,809 SNPs from transcriptome sequences. In addition to concatenated and coalescence-based approaches for phylogenetic inference, we also reconstructed 256 gene topologies to investigate conflict among nuclear genes. Our results show that the conflicts arise mainly from the relationship between Lithocarpus and Quercus, with approximately 34% of genes supporting the two genera as a sister group. We also try to understand why the genes of minority topologies are different from those of majority topologies. To answer the question, we performed a functional enrichment analysis to determine the function of the minority topological genes. According to the GO terms, their functions are primarily related to cellular structure or organelle. In the following step, we will investigate whether the main sources of discordance are introgression, incomplete lineage sorting, or selection.

There is an interesting relation between the quantum periods on a certain limit of local P1×P1 Calabi-Yau space and a TBA (Thermodynamic Bethe Ansatz) system appeared in the studies of ABJM (Aharony-Bergman-Jafferis-Maldacena) theory. We propose a one-parameter generalization of the relation. Furthermore, we derive the differential operators for quantum periods and the TBA-like equation in various limits of the generalized relation.

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited eye disease. In our previous investigations, we have reported the spectrum and frequency of mitochondrial MT-ND1, MT-ND4 and MT-ND6 gene in Chinese LHON population. This study aimed to assess the molecular epidemiology of MT-TT mutations in Chinese families with LHON. A cohort of 352 Chinese Han probands lacking the known LHON-associated mtDNA mutations and 376 control subjects underwent molecular analysis of mtDNA. All variants were evaluated for evolutionary conservation, structural and functional consequences. Fifteen variants were identified in the MT-TT gene by mitochondrial genome analysis of LHON pedigrees, which was substantially higher than that of individuals from general Chinese populations. The incidences of the two known LHON-associated mutations, m.15927G > A and m.15951A > G, were 2.27% and 1.14%, respectively. Nine putative LHON-associated variants were identified in 20 probands, translated into 2.1% cases of this cohort. Moreover, mtDNAs in 41 probands carrying the MT-TT mutation(s) were widely dispersed among nine Eastern Asian haplogroups. Our results suggest that the MT-TT gene is a mutational hotspot for these 352 Chinese families lacking the known LHON-associated mutations. These data further showed the molecular epidemiology of MT-TT mutations in Chinese Han LHON pedigrees.

Many breast cancer patients suffer from obvious side effects induced by chemotherapy. Formononetin (FM), one kind ingredient of Chinese herbal medicine, has been suggested to inhibit MCF-7 breast cancer cells. And recently metformin (MET) has gained more attention as a potential anti-cancer drug. The aim of this study was to investigate the synergistic effects of FM and MET on the proliferation of MCF-7 cells and to clarify the possible molecular mechanism involved. MCF-7 cells were treated with various concentrations of FM (40 and 80 μM) or FM (40 and 80 μM) combined with MET (150 μM) for 48 h. Cell proliferation was tested by an methyl tetrazolium (MTT) (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay. The percentage of apoptotic cells was measured by flow cytometry. The expression level of b-cell lymphoma/leukemia-2 (bcl-2) mRNA was examined by RT-PCR, while the expression levels of phosphorylated extracellular signal-regulated kinases (p-ERK1/2) and bcl-2 protein were detected by Western blotting. Compared with untreated cells, 40 μM and 80 μM FM efficiently inhibited proliferation and increased apoptosis in MCF-7 cells. Additionally, 40 μM and 80 μM FM greatly downregulated bcl-2 mRNA expression when compared with untreated cells. Furthermore, the protein expression of bcl-2 and p-ERK1/2 was significantly reduced by 40 μM and 80 μM FM. The cytotoxic effect of FM was more remarkable when 150 μM MET was added. Taken together, the combinational use of FM and MET enhanced cell growth inhibition, and the induction of apoptosis in MCF-7 cells mediated by the ERK1/2 signaling pathway.

To identify the possible quarantine viruses in seven common sunflower varieties imported from the United States of America and the Netherlands, we tested total RNAs extracted from the leaf tissues using next-generation sequencing of small RNAs. After analysis of small RNA sequencing data, no any quarantine virus was found, but a double-stranded RNA (dsRNA) molecule showing typical genomic features of endornavirus was detected in two varieties, X3939 and SH1108. Full-length sequence and phylogenetic analysis showed that it is a novel endornavirus, temporarily named as Helianthus annuus alphaendornavirus (HaEV). Its full genome corresponds to a 14 662-bp dsRNA segment, including a 21-nt 5' untranslated region (UTR), 3' UTR ending with the unique sequence CCCCCCCC and lacking a poly(A) tail. An open reading frame (ORF) that encodes a deduced 4 867 amino acids (aa) polyprotein with three domains: RdRP, Hel and UGT (UDP-glycosyltransferase). HaEV mainly distributed in the cytoplasm but less in the nucleus of leaf cells by fluorescence in situ hybridization (FISH) experiment. This virus has a high seed infection rate in the five varieties, X3907, X3939, A231, SH1108 and SR1320. To our knowledge, this is the first report about the virus of the family Endornaviridae in the common sunflower.

Abstract Göttsche-Nakajima-Yoshioka K-theoretic blowup equations characterize the Nekrasov partition function of five dimensional N = 1 $$ \mathcal{N}=1 $$ supersymmetric gauge theories compactified on a circle, which via geometric engineering correspond to the refined topological string theory on SU(N) geometries. In this paper, we study the K-theoretic blowup equations for general local Calabi-Yau threefolds. We find that both vanishing and unity blowup equations exist for the partition function of refined topological string, and the crucial ingredients are the r fields introduced in our previous paper. These blowup equations are in fact the functional equations for the partition function and each of them results in infinite identities among the refined free energies. Evidences show that they can be used to determine the full refined BPS invariants of local Calabi-Yau threefolds. This serves an independent and sometimes more powerful way to compute the partition function other than the refined topological vertex in the A-model and the refined holomorphic anomaly equations in the B-model. We study the modular properties of the blowup equations and provide a procedure to determine all the vanishing and unity r fields from the polynomial part of refined topological string at large radius point. We also find that certain form of blowup equations exist at generic loci of the moduli space.

Abstract Background Divergent genetic responses to the same environmental pressures may lead sympatric ecological speciation possible. Such speciation process possibly explains rapid sympatric speciation of island species. Two island endemic ginger species Zingiber kawagoii and Z. shuanglongensis was suggested to be independently originated from inland ancestors, but their island endemism and similar morphologies and habitats lead another hypothesis of in situ ecological speciation. For understanding when and how these two species diverged, intraspecific variation was estimated from three chloroplast DNA fragments (cpDNA) and interspecific genome-wide SNPs and expression differences after saline treatment were examined by transcriptomic analyses. Results Extremely low intraspecific genetic variation was estimated by cpDNA sequences in both species: nucleotide diversity π = 0.00002 in Z. kawagoii and no nucleotide substitution but only indels found in Z. shuanglongensis. Nonsignificant inter-population genetic differentiation suggests homogenized genetic variation within species. Based on 53,683 SNPs from 13,842 polymorphic transcripts, in which 10,693 SNPs are fixed between species, Z. kawagoii and Z. shuanglongensis were estimated to be diverged since 218~ 238 thousand generations ago (complete divergence since 41.5~ 43.5 thousand generations ago). This time is more recent than the time of Taiwan Island formation. In addition, high proportion of differential expression genes (DEGs) is non-polymorphic or non-positively selected, suggesting key roles of plastic genetic divergence in broaden the selectability in incipient speciation. While some positive selected DEGs were mainly the biotic and abiotic stress-resistance genes, emphasizing the importance of adaptive divergence of stress-related genes in sympatric ecological speciation. Furthermore, the higher proportional expression of functional classes in Z. kawagoii than in Z. shuanglongensis explains the more widespread distribution of Z. kawagoii in Taiwan. Conclusions Our results contradict the previous hypothesis of independent origination of these two island endemic ginger species from SE China and SW China. Adaptive divergent responses to the stress explain how these gingers maintain genetic differentiation in sympatry. However, the recent speciation and rapid expansion make extremely low intraspecific genetic variation in these two species. This study arise a more probable speciation hypothesis of sympatric speciation within an island via the mutation-order mechanism underlying the same environmental pressure.

The renewal of temperate coniferous forests has a high impact on the global climate, as well as the survival of forest wildlife. As an important native afforestation tree species in northern China, Mongolian pine (Pinus sylvestris L. var. mongolica Litv.) is facing the dilemma of severe regeneration and forest growth. External factors, such as natural disturbances or human intervention, may affect the forest growth potential. Therefore, the present study explores whether environmental factors and afforestation methods affect the growth increment of Mongolian pine. To answer the question mentioned above, natural forest and two kinds of afforestation forests are included in this study. The growth increment is calculated by measuring basic growth parameters. A linear mixed-effect model is used to test whether surface fire, accompanying birch, edge effect, afforestation method, and tree age were determinants of the growth increment. With the model selection, the tree age combined with fire or afforestation is determined as significant effects on the growth increment. The effects of growth position and accompanying plants only influenced young pines. The effects decrease with age, implying the resource competition occurs at young ages only but not affect the adults of dominance trees. Since the growth rate of Mongolian pine varies with age, the environmental selection of timber volume is age-dependent. However, we also found that the growth increment slowdowns if too-fast growth investment in secondary growth at a young. Strengthening the competitive pressure of seedling afforestation is conducive to selecting individuals with a high growth increment and delayed growth cessation. Accordingly, fast-growing trees that survive fires are recommended as sources of seed-harvesting mother trees. Sowing afforestation that is easier to adjust the growth rate of seedlings is recommended than the seedling afforestation. Since external disturbances underlie the age-dependent selection of Mongolian pine growth, competition and environmental pressures at a young age are beneficial for prolonging the growth period and increasing timber volume accumulation. From this study, it can be seen that moderate fire disturbance and the selection of seed from healthy trees for tending are beneficial to the regeneration of temperate coniferous trees and the maintenance of healthy forests.

The pathophysiology underlying spiral ganglion cell defect–induced deafness remains elusive. Using the whole exome sequencing approach, in combination with functional assays and a mouse disease model, we identified the potentially novel deafness-causative MAP1B gene encoding a highly conserved microtubule-associated protein. Three novel heterozygous MAP1B mutations (c.4198A>G, p.1400S>G; c.2768T>C, p.923I>T; c.5512T>C, p.1838F>L) were cosegregated with autosomal dominant inheritance of nonsyndromic sensorineural hearing loss in 3 unrelated Chinese families. Here, we show that MAP1B is highly expressed in the spiral ganglion neurons in the mouse cochlea. Using otic sensory neuron–like cells, generated by pluripotent stem cells from patients carrying the MAP1B mutation and control subject, we demonstrated that the p.1400S>G mutation caused the reduced levels and deficient phosphorylation of MAP1B, which are involved in the microtubule stability and dynamics. Strikingly, otic sensory neuron–like cells exhibited disturbed dynamics of microtubules, axonal elongation, and defects in electrophysiological properties. Dysfunctions of these derived otic sensory neuron–like cells were rescued by genetically correcting MAP1B mutation using CRISPR/Cas9 technology. Involvement of MAP1B in hearing was confirmed by audiometric evaluation of Map1b heterozygous KO mice. These mutant mice displayed late-onset progressive sensorineural hearing loss that was more pronounced in the high frequencies. The spiral ganglion neurons isolated from Map1b mutant mice exhibited the deficient phosphorylation and disturbed dynamics of microtubules. Map1b deficiency yielded defects in the morphology and electrophysiology of spiral ganglion neurons, but it did not affect the morphologies of cochlea in mice. Therefore, our data demonstrate that dysfunctions of spiral ganglion neurons induced by MAP1B deficiency caused hearing loss.

The mitochondrial ADP/ATP carrier (AAC) exports ATP and imports ADP through alternating between cytosol-open (c-) and matrix-open (m-) states. The salt bridge networks near the matrix side (m-gate) and cytosol side (c-gate) are thought to be crucial for state transitions, yet our knowledge on these networks is still limited. In the current work, we focus on more conserved m-gate network in the c-state AAC. All-atom molecular dynamics (MD) simulations on a variety of mutants and the CATR-AAC complex have revealed that: (1) without involvement of other positive residues, the charged residues from the three Px[DE]xx[KR] motifs only are prone to form symmetrical inter-helical network; (2) R235 plays a determinant role for the asymmetry in m-gate network of AAC; (3) R235 significantly strengthens the interactions between H3 and H5; (4) R79 exhibits more significant impact on m-gate than R279; (5) CATR promotes symmetry in m-gate mainly through separating R234 from D231 and fixing R79; (6) vulnerability of the H2-H3 interface near matrix side could be functionally important. Our results provide new insights into the highly conserved yet variable m-gate network in the big mitochondrial carrier family.