Elastic stable intramedullary nail combined with Kirschner wire (E-K) technique for treating pediatric distal tibial diaphyseal metaphyseal junction (DTDMJ) fractures.

Objective: Elastic stable intramedullary nail (ESIN) is a commonly used method for treating diaphyseal fractures of the tibia, but its application in Distal Tibial Diaphyseal Metaphyseal Junction (DTDMJ) fractures has been a subject of controversy. This study aims to evaluate the clinical efficacy of the Elastic stable intramedullary nail-Kirschner wire (E-K) technique in treating pediatric DTDMJ fractures, providing better clinical decision-making for clinicians in diagnosing and treating such fractures. Methods: We conducted a retrospective analysis of patients aged 3-9 years who received treatment at our hospital from January 2019-January 2021 for distal tibial diaphyseal metaphyseal junction (DTDMJ) fractures. Based on their surgical procedures, they were categorized into the Elastic Stable Intramedullary Nail-Kirschner wire group (E-K) and the ESIN group. Demographic data, surgical duration, clinical outcomes, complications, and imaging data were recorded. Results: The study included a total of 57 patients, with 24 cases in the E-K group and 33 cases in the ESIN group. There were 30 males and 27 females. The average age was (6.25 ± 1.59) years in the E-K group and (6.27 ± 1.48) years in the ESIN group. There were no significant differences between the two groups in terms of gender, age, weight, time from injury to surgery, follow-up time, side of injury, associated injuries, nail site infection, deep infection, and nail removal time (P > 0.05). Neither group experienced nonunion or refracture. The E-K group exhibited significantly lower coronal and sagittal plane angular values at the final follow-up compared to the ESIN group (P < 0.001). In the E-K group, the final follow-up coronal plane angle was 2.67 (1.09)°, while in the ESIN group, it was 6.55 (2.05)°. The final follow-up sagittal plane angle was 3.12 (1.54)° in the E-K group and 7.58 (1.48)° in the ESIN group. Both groups showed good alignment in the initial postoperative x-rays, with no statistically significant differences. However, during clinical healing, the ESIN group exhibited significant displacement, whereas the E-K group had minimal displacement, demonstrating a significant statistical difference (P < 0.001). There was a statistically significant difference in the AOFAS joint function assessment between the two groups (P = 0.027). Conclusion: The E-K technique is a viable option for treating DTDMJ fractures in pediatric patients, with well-established clinical efficacy. Its advantages include a straightforward surgical procedure, safety, and a low incidence of severe complications.

ZMIZ1::ABL1 Fusion: An Uncommon Molecular Event With Clinical Implications in Pediatric Cancer.

CONTEXT.­: Pediatric B-cell acute lymphoblastic leukemia is genetically and phenotypically heterogeneous, with a genetic landscape including chromosomal translocations that disrupt ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1). OBJECTIVE.­: To characterize an uncommon chromosomal translocation in acute leukemia. DESIGN.­: Genetic testing, including karyotype and fluorescence in situ hybridization (FISH) analysis, was used to determine the underlying genetic aberration driving the disorder and to guide disease classification and risk stratification. More-detailed testing using RNA sequencing was performed, based on the results from these assays. Three-dimensional molecular modeling was used to visualize the impact of aberrant fused transcripts identified by transcriptome profiling. RESULTS.­: Karyotype analysis of the bone marrow demonstrated a complex karyotype with, most notably, a t(9;10)(q34.1;q22) translocation. ABL1 break-apart probe FISH findings supported ABL1 disruption. Bone marrow transcriptome analysis revealed mutant ZMIZ1::ABL1 (ZMIZ1, zinc finger MIZ-type containing 1) fusion transcripts as a consequence of t(9;10)(q34.1;q22). Three-dimensional modeling of the mutant ZMIZ1::ABL1 fusion protein confirmed an altered ABL1 protein structure compared to that of the wild type, suggesting a constitutively active conformation. CONCLUSIONS.­: The t(9;10) translocation resulting in ZMIZ1::ABL1 fusion transcripts is an uncommon form of BCR::ABL1-like (BCR, BCR activator of RhoGEF and GTPase) acute lymphoblastic leukemia. Although the karyotype was complex, identifying the t(9;10)(q34.1;q22) translocation, ABL1 disruption, and ZMIZ1::ABL1 transcript enabled effective ABL1-targeted treatment. Our data support the use of tyrosine kinase inhibitors to treat ZMIZ1::ABL1-derived B-cell acute lymphoblastic leukemia.

Fabrication of lignosulfonate-derived porous carbon via pH-tunable self-assembly strategy for efficient atrazine removal.

Herein, a straightforward protocol was developed for the one-pot synthesis of N-doped lignosulfonate-derived carbons (NLDCs) with a tunable porous structure using natural amino acids-templated self-assembly strategy. Specifically, histidine was employed as a template reagent, leading to the preparation of 10-NLDC-21 with remarkable characteristics, including the large specific surface area (SBET = 1844.5 m2/g), pore volume (Vmes = 1.22 cm3/g) and efficient adsorption for atrazine (ATZ) removal. The adsorption behavior of ATZ by NLDCs followed the Langmuir and pseudo-second-order models, suggesting a monolayer chemisorption nature of ATZ adsorption with the maximum adsorption capacity reached up to 265.77 mg/g. Furthermore, NLDCs exhibited excellent environmental adaptability and recycling performance. The robust affinity could be attributed to multi-interactions including pore filling, electrostatic attraction, hydrogen bonding and π-π stacking between the adsorbents and ATZ molecules. This approach offers a practical method for exploring innovative bio-carbon materials for sewage treatment.

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole sporozoite PfSPZ Vaccine in African infants. Innate immune activation and myeloid signatures at pre-vaccination baseline correlated with protection from Pf parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ Vaccine dose. Machine learning identified spliceosome, proteosome, and resting dendritic cell signatures as pre-vaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline CSP-specific IgG predicted non-protection. Pre-vaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T-cell responses post-vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naïve mice while diminishing the CD8+ T-cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity of whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggest that PfSPZ Vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

MPRAVarDB: an online database and web server for exploring regulatory effects of genetic variants.

Massively parallel reporter assay (MPRA) is an important technology to evaluate the impact of genetic variants on gene regulation. Here, we present MPRAVarDB, an online database and web server, for exploring regulatory effects of genetic variants. MPRAVarDB harbors 18 MPRA experiments designed to assess the regulatory effects of genetic variants associated with GWAS loci, eQTLs and various genomic features, resulting in a total of 242,818 variants tested across more than 30 cell lines and 30 human diseases or traits. MPRAVarDB empowers the query of MPRA variants by genomic region, disease and cell line or by any combination of these query terms. Notably, MPRAVarDB offers a suite of pretrained machine learning models tailored to the specific disease and cell line, facilitating the genome-wide prediction of regulatory variants. MPRAVarDB is friendly to use, and users only need a few clicks to receive query and prediction results.

Genomes of Meniocus linifolius and Tetracme quadricornis reveal the ancestral karyotype and genomic features of core Brassicaceae.

Brassicaceae represents an important plant family from both a scientific and economic perspective. However, genomic features related to the early diversification of this family have not been fully characterized, especially upon the uplift of the Tibetan Plateau, which was followed by increasing aridity in the Asian interior, intensifying monsoons in Eastern Asia, and significantly fluctuating daily temperatures. Here, we reveal the genomic architecture that accompanied early Brassicaceae diversification by analyzing two high-quality chromosome-level genomes for Meniocus linifolius (Arabodae; clade D) and Tetracme quadricornis (Hesperodae; clade E), together with genomes representing all major Brassicaceae clades and the basal Aethionemeae. We reconstructed an ancestral core Brassicaceae karyotype (CBK) containing 9 pseudochromosomes with 65 conserved syntenic genomic blocks and identified 9702 conserved genes in Brassicaceae. We detected pervasive conflicting phylogenomic signals accompanied by widespread ancient hybridization events, which correlate well with the early divergence of core Brassicaceae. We identified a successive Brassicaceae-specific expansion of the class I TREHALOSE-6-PHOSPHATE SYNTHASE 1 (TPS1) gene family, which encodes enzymes with essential regulatory roles in flowering time and embryo development. The TPS1s were mainly randomly amplified, followed by expression divergence. Our results provide fresh insights into historical genomic features coupled with Brassicaceae evolution and offer a potential model for broad-scale studies of adaptive radiation under an ever-changing environment.

Genome assemblies of 11 bamboo species highlight diversification induced by dynamic subgenome dominance.

Polyploidy (genome duplication) is a pivotal force in evolution. However, the interactions between parental genomes in a polyploid nucleus, frequently involving subgenome dominance, are poorly understood. Here we showcase analyses of a bamboo system (Poaceae: Bambusoideae) comprising a series of lineages from diploid (herbaceous) to tetraploid and hexaploid (woody), with 11 chromosome-level de novo genome assemblies and 476 transcriptome samples. We find that woody bamboo subgenomes exhibit stunning karyotype stability, with parallel subgenome dominance in the two tetraploid clades and a gradual shift of dominance in the hexaploid clade. Allopolyploidization and subgenome dominance have shaped the evolution of tree-like lignified culms, rapid growth and synchronous flowering characteristic of woody bamboos as large grasses. Our work provides insights into genome dominance in a remarkable polyploid system, including its dependence on genomic context and its ability to switch which subgenomes are dominant over evolutionary time.

Functional 3'-UTR Variants Identify Regulatory Mechanisms Impacting Alcohol Use Disorder and Related Traits.

Although genome-wide association studies (GWAS) have identified loci associated with alcohol consumption and alcohol use disorder (AUD), they do not identify which variants are functional. To approach this, we evaluated the impact of variants in 3' untranslated regions (3'-UTRs) of genes in loci associated with substance use and neurological disorders using a massively parallel reporter assay (MPRA) in neuroblastoma and microglia cells. Functionally impactful variants explained a higher proportion of heritability of alcohol traits than non-functional variants. We identified genes whose 3'UTR activities are associated with AUD and alcohol consumption by combining variant effects from MPRA with GWAS results. We examined their effects by evaluating gene expression after CRISPR inhibition of neuronal cells and stratifying brain tissue samples by MPRA-derived 3'-UTR activity. A pathway analysis of differentially expressed genes identified inflammation response pathways. These analyses suggest that variation in response to inflammation contributes to the propensity to increase alcohol consumption.

Comprehensive landscape-style investigation of the molecular mechanism of acupuncture at ST36 single acupoint on different systemic diseases.

The principle of acupoint stimulation efficacy is based on traditional meridian theory. However, the molecular mechanisms underlying the therapeutic effects of acupoints in treating diseases remain unclear in modern scientific understanding. In this study, we selected the ST36 acupoint for investigation and summarized all relevant literature from the PubMed database over the past 10 years. The results indicate that stimulation of ST36 single acupoints has therapeutic effects mainly in models of respiratory, neurological, digestive, endocrine and immune system diseases. And it can affect the inflammatory state, oxidative stress, respiratory mucus secretion, intestinal flora, immune cell function, neurotransmitter transmission, hormone secretion, the network of Interstitial Cells of Cajal (ICC) and glucose metabolism of the organism in these pathological states. Among them, acupuncture at the ST36 single point has the most prominent function in regulating the inflammatory state, which can mainly affect the activation of MAPK signaling pathway and drive the "molecular-cellular" mode involving macrophages, T-lymphocytes, mast cells (MCs) and neuroglial cells as the core to trigger the molecular level changes of the acupuncture point locally or in the target organ tissues, thereby establishing a multi-system, multi-target, multi-level molecular regulating mechanism. This article provides a comprehensive summary and discussion of the molecular mechanisms and effects of acupuncture at the ST36 acupoint, laying the groundwork for future in-depth research on acupuncture point theory.

Structural Basis of Nucleic Acid Recognition and 6mA Demethylation by Caenorhabditis elegans NMAD-1A.

N6-methyladenine (6mA) of DNA is an emerging epigenetic mark in the genomes of Chlamydomonas, Caenorhabditis elegans, and mammals recently. Levels of 6mA undergo drastic fluctuation and thus affect fertility during meiosis and early embryogenesis. Here, we showed three complex structures of 6mA demethylase C. elegans NMAD-1A, a canonical isoform of NMAD-1 (F09F7.7). Biochemical results revealed that NMAD-1A prefers 6mA Bubble or Bulge DNAs. Structural studies of NMAD-1A revealed an unexpected "stretch-out" conformation of its Flip2 region, a conserved element that is usually bent over the catalytic center to facilitate substrate base flipping in other DNA demethylases. Moreover, the wide channel between the Flip1 and Flip2 of the NMAD-1A explained the observed preference of NMAD-1A for unpairing substrates, of which the flipped 6mA was primed for catalysis. Structural analysis and mutagenesis studies confirmed that key elements such as carboxy-terminal domain (CTD) and hypothetical zinc finger domain (ZFD) critically contributed to structural integrity, catalytic activity, and nucleosome binding. Collectively, our biochemical and structural studies suggest that NMAD-1A prefers to regulate 6mA in the unpairing regions and is thus possibly associated with dynamic chromosome regulation and meiosis regulation.

Flexible Transparent Electrode Based on Ag Nanowires: Ag Nanoparticles Co-Doped System for Organic Light-Emitting Diodes.

Flexible organic light-emitting diodes (FOLEDs) have promising potential for future wearable applications because of their exceptional mechanical flexibility. Silver nanowire (Ag NW) networks are the most promising candidates to replace indium tin oxide (ITO), which is limited by its poor bendability. In this study, three different methods including methanol impregnation, argon plasma treatment, and ultraviolet radiation were used to reduce the junction resistance of Ag NWs to optimize the flexible transparent electrodes (FTEs); which were prepared using Ag NWs and poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS). Then, the optoelectronic properties of the FTEs were further improved by using a co-doped system of silver nanowires and silver nanoparticles (Ag NPs), the structure of which consisted of PET/Ag NWs: Ag NPs/PEDOT: PSS/DMSO. The largest FOM value of 1.42 × 10-2 ohm-1 and a low sheet resistance value of 13.86 ohm/sq were obtained using the optimized FTEs. The prepared FOLED based on the optimized FTEs had a luminous efficiency of 6.04 cd/A and a maximum EQE of 1.92%, and exhibited no observed decline in efficiency when reaching maximum luminance. After 500 bending tests, the luminance still reached 82% of the original value. It is demonstrated that the FTEs prepared via the co-doped system have excellent optoelectronic properties as well as high mechanical stability.

The Optimization of Hole Injection Layer in Organic Light-Emitting Diodes.

Organic light-emitting diodes (OLEDs) are widely recognized as the forefront technology for displays and lighting technology. Now, the global OLED market is nearly mature, driven by the rising demand for superior displays in smartphones. In recent years, numerous strategies have been introduced and demonstrated to optimize the hole injection layer to further enhance the efficiency of OLEDs. In this paper, different methods of optimizing the hole injection layer were elucidated, including using a suitable hole injection material to minimize the hole injection barrier and match the energy level with the emission layer, exploring new preparation methods to optimize the structure of hole injection layer, and so on. Meanwhile, this article can help people to understand the current research progress and the challenges still faced in relation to the hole injection layer in OLEDs, providing future research directions to enhance the properties of OLEDs.

Temperature Compensation of Laser Methane Sensor Based on a Large-Scale Dataset and the ISSA-BP Neural Network.

We aimed to improve the detection accuracy of laser methane sensors in expansive temperature application environments. In this paper, a large-scale dataset of the measured concentration of the sensor at different temperatures is established, and a temperature compensation model based on the ISSA-BP neural network is proposed. On the data side, a large-scale dataset of 15,810 sets of laser methane sensors with different temperatures and concentrations was established, and an Improved Isolation Forest algorithm was used to clean the large-scale data and remove the outliers in the dataset. On the modeling framework, a temperature compensation model based on the ISSA-BP neural network is proposed. The quasi-reflective learning, chameleon swarm algorithm, Lévy flight, and artificial rabbits optimization are utilized to improve the initialization of the sparrow population, explorer position, anti-predator position, and position of individual sparrows in each generation, respectively, to improve the global optimization seeking ability of the standard sparrow search algorithm. The ISSA-BP temperature compensation model far outperforms the four models, SVM, RF, BP, and PSO-BP, in model evaluation metrics such as MAE, MAPE, RMSE, and R-square for both the training and test sets. The results show that the algorithm in this paper can significantly improve the detection accuracy of the laser methane sensor under the wide temperature application environment.

Ionic Liquid/Water Binary Solvent Anti-Freezing Hydrogel for Strain and Temperature Sensors.

Hydrogels are widely applied in the flexible wearable electronic devices field owing to their skin-like stretchability, superb biocompatibility, and high conductivity retention under mechanical deformations. Nevertheless, hydrogels are prone to freezing at low temperatures and losing water at high temperatures, which seriously limits their practical applications. Herein, a binary solvent system of ionic liquid (1-ethyl-3-methylimidazolium chloride) and water was prepared to endow the ionic hydrogel high ionic conductivity (0.28 S m-1 at 25 °C), high transparency (94.26%), and superior freezing tolerance (-50 °C). The multiple hydrogen bonds formed among polymer chains, water, and ionic liquids significantly improved the mechanical properties of the ionic hydrogel, enabling excellent tensile properties (strain >1800%) and durability (1000 times at 100% strain). Moreover, the ionic hydrogel was further assembled into a dual-response sensor, which exhibited satisfactory sensitivity to both tension (gauge factor = 2.15 at 200% strain) and temperature (temperature coefficient of resistance = -1.845%/°C) and can be applied for human motion and body temperature monitoring. This study provides a versatile method for preparing multifunctional hydrogels with a wide range of applications and lays the groundwork for human movement detection and smart health care.

Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene.

Single-cell transcriptomics studies have begun to identify breast epithelial cell and stromal cell specific transcriptome differences between BRCA1/2 mutation carriers and non-carriers. We generated a single-cell transcriptome atlas of breast tissues from BRCA1, BRCA2 mutation carriers and compared this single-cell atlas of mutation carriers with our previously described single-cell breast atlas of healthy non-carriers. We observed that BRCA1 but not BRCA2 mutations altered the ratio between basal (basal-myoepithelial), luminal progenitor (luminal adaptive secretory precursor, LASP), and mature luminal (luminal hormone sensing) cells in breast tissues. A unique subcluster of cells within LASP cells is underrepresented in case of BRCA1 and BRCA2 mutation carriers compared with non-carriers. Both BRCA1 and BRCA2 mutations specifically altered transcriptomes in epithelial cells which are an integral part of NFκB, LARP1, and MYC signaling. Signaling pathway alterations in epithelial cells unique to BRCA1 mutations included STAT3, BRD4, SMARCA4, HIF2A/EPAS1, and Inhibin A signaling. BRCA2 mutations were associated with upregulation of IL6, PDK1, FOXO3, and TNFSF11 signaling. These signaling pathway alterations are sufficient to alter sensitivity of BRCA1/BRCA2-mutant breast epithelial cells to transformation as epithelial cells from BRCA1 mutation carriers overexpressing hTERT + PIK3CAH1047R generated adenocarcinomas, whereas similarly modified mutant BRCA2 cells generated basal carcinomas in NSG mice. Thus, our studies provide a high-resolution transcriptome atlas of breast epithelial cells of BRCA1 and BRCA2 mutation carriers and reveal their susceptibility to PIK3CA mutation-driven transformation. SIGNIFICANCE: This study provides a single-cell atlas of breast tissues of BRCA1/2 mutation carriers and demonstrates that aberrant signaling due to BRCA1/2 mutations is sufficient to initiate breast cancer by mutant PIK3CA.

Enhancing epidural needle guidance using a polarization-sensitive optical coherence tomography probe with convolutional neural networks.

Epidural anesthesia helps manage pain during different surgeries. Nonetheless, the precise placement of the epidural needle remains a challenge. In this study, we developed a probe based on polarization-sensitive optical coherence tomography (PS-OCT) to enhance the epidural anesthesia needle placement. The probe was tested on six porcine spinal samples. The multimodal imaging guidance used the OCT intensity mode and three distinct PS-OCT modes: (1) phase retardation, (2) optic axis, and (3) degree of polarization uniformity (DOPU). Each mode enabled the classification of different epidural tissues through distinct imaging characteristics. To further streamline the tissue recognition procedure, convolutional neural network (CNN) were used to autonomously identify the tissue types within the probe's field of view. ResNet50 models were developed for all four imaging modes. DOPU imaging was found to provide the highest cross-testing accuracy of 91.53%. These results showed the improved precision by PS-OCT in guiding epidural anesthesia needle placement.

Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank.

BACKGROUND: In the United States, ~50% of individuals who meet criteria for alcohol use disorder (AUD) during their lifetimes do not remit. We previously reported that a polygenic score for AUD (PGSAUD ) was positively associated with AUD severity as measured by DSM-5 lifetime criterion count, and AUD severity was negatively associated with remission. Thus, we hypothesized that PGSAUD would be negatively associated with remission. METHODS: Individuals of European (EA) and African ancestry (AA) from the Collaborative Study on the Genetics of Alcoholism (COGA) who met lifetime criteria for AUD, and two EA cohorts ascertained for studies of liver diseases and substance use disorders from the Indiana Biobank were included. In COGA, 12-month remission was defined as any period of ≥12 consecutive months without meeting AUD criteria except craving and was further categorized as abstinent and non-abstinent. In the Indiana Biobank, remission was defined based on ICD codes and could not be further distinguished as abstinent or non-abstinent. Sex and age were included as covariates. COGA analyses included additional adjustment for AUD severity, family history of remission, and AUD treatment history. RESULTS: In COGA EA, PGSAUD was negatively associated with 12-month and non-abstinent remission (p ≤ 0.013, ßs between -0.15 and -0.10) after adjusting for all covariates. In contrast to the COGA findings, PGSAUD was positively associated with remission (p = 0.004, ß = 0.28) in the Indiana Biobank liver diseases cohort but not in the Indiana Biobank substance use disorder cohort (p = 0.17, ß = 0.15). CONCLUSIONS: PGSAUD was negatively associated with 12-month and non-abstinent remission in COGA EA, independent of behavioral measures of AUD severity and family history of remission. The discrepant results in COGA and the Indiana Biobank could reflect different ascertainment strategies: the Indiana Biobank participants were older and had higher rates of liver disease, suggesting that these individuals remitted due to alcohol-related health conditions that manifested in later life.

Identifying Genes Associated with Alzheimer's Disease Using Gene-Based Polygenic Risk Score.

BACKGROUND: Except APOE, Alzheimer's disease (AD) associated genes identified in recent large-scale genome-wide association studies (GWAS) had small effects and explained a small portion of heritability. Many AD-associated genes have even smaller effects thereby sub-threshold p-values in large-scale GWAS and remain to be identified. For some AD-associated genes, drug targeting them may have limited efficacies due to their small effect sizes. OBJECTIVE: The purpose of this study is to identify AD-associated genes with sub-threshold p-values and prioritize drugs targeting AD-associated genes that have large efficacies. METHODS: We developed a gene-based polygenic risk score (PRS) to identify AD genes. It was calculated using SNPs located within genes and having the same directions of effects in different study cohorts to exclude cohort-specific findings and false positives. Gene co-expression modules and protein-protein interaction networks were used to identify AD-associated genes that interact with multiple other genes, as drugs targeting them have large efficacies via co-regulation or interactions. RESULTS: Gene-based PRS identified 389 genes with 164 of them not previously reported as AD-associated. These 389 genes explained 56.12% -97.46% SNP heritability; and they were enriched in brain tissues and 164 biological processes, most of which are related to AD and other neurodegenerative diseases. We prioritized 688 drugs targeting 64 genes that were in the same co-expression modules and/or PPI networks. CONCLUSIONS: Gene-based PRS is a cost-effective way to identify AD-associated genes without substantially increasing the sample size. Co-expression modules and PPI networks can be used to identify drugs having large efficacies.

Five new and noteworthy species of Epidendroideae (Orchidaceae) from southwestern China based on morphological and phylogenetic evidence.

Five new orchid species from southwestern China's Yunnan Province and the Tibetan Autonomous Region, Neottialihengiae, Neottiachawalongensis, Papilionanthemotuoensis, Gastrochiluslihengiae, and Gastrochilusbernhardtianus, are described and illustrated. To confirm their identities, and to resolve phylogenetic relationships, we sequenced the complete plastomes of these taxa with their congeneric species, adding new plastomes of three Neottia species, two Papilionanthe species and nine Gastrochilus species. Combined with published plastid sequences, our well-resolved phylogeny supported the alliance of N.lihengiae with the the N.grandiflora + N.pinetorum clade. Neottiachawalongensis is now sister to N.alternifolia, while P.motuoensis is closely related to P.subulata + P.teres. Conversely, phylogenetic analyses based on complete plastomes and plastid sequences showed inconsistent relationships among taxa in the genus Gastrochilus, but the two new species, G.lihengiae and G.bernhardtianus were supported by all datasets.