Ensemble species distribution modeling and multilocus phylogeography provide insight into the spatial genetic patterns and distribution dynamics of a keystone forest species, Quercus glauca.

BACKGROUND: Forests are essential for maintaining species diversity, stabilizing local and global climate, and providing ecosystem services. Exploring the impact of paleogeographic events and climate change on the genetic structure and distribution dynamics of forest keystone species could help predict responses to future climate change. In this study, we combined an ensemble species distribution model (eSDM) and multilocus phylogeography to investigate the spatial genetic patterns and distribution change of Quercus glauca Thunb, a keystone of East Asian subtropical evergreen broad-leaved forest. RESULTS: A total of 781 samples were collected from 77 populations, largely covering the natural distribution of Q. glauca. The eSDM showed that the suitable habitat experienced a significant expansion after the last glacial maximum (LGM) but will recede in the future under a general climate warming scenario. The distribution centroid will migrate toward the northeast as the climate warms. Using nuclear SSR data, two distinct lineages split between east and west were detected. Within-group genetic differentiation was higher in the West than in the East. Based on the identified 58 haplotypes, no clear phylogeographic structure was found. Populations in the Nanling Mountains, Wuyi Mountains, and the southwest region were found to have high genetic diversity. CONCLUSIONS: A significant negative correlation between habitat stability and heterozygosity might be explained by the mixing of different lineages in the expansion region after LGM and/or hybridization between Q. glauca and closely related species. The Nanling Mountains may be important for organisms as a dispersal corridor in the west-east direction and as a refugium during the glacial period. This study provided new insights into spatial genetic patterns and distribution dynamics of Q. glauca.

EEF1A2 mutations in epileptic encephalopathy/intellectual disability: Understanding the potential mechanism of phenotypic variation.

EEF1A2 encodes protein elongation factor 1-alpha 2, which is involved in Guanosine triphosphate (GTP)-dependent binding of aminoacyl-transfer RNA (tRNA) to the A-site of ribosomes during protein biosynthesis and is highly expressed in the central nervous system. De novo mutations in EEF1A2 have been identified in patients with extensive neurological deficits, including intractable epilepsy, globe developmental delay, and severe intellectual disability. However, the mechanism underlying phenotype variation is unknown. Using next-generation sequencing, we identified a novel and a recurrent de novo mutation, c.294C>A; p.(Phe98Leu) and c.208G>A; p.(Gly70Ser), in patients with Lennox-Gastaut syndrome. The further systematic analysis revealed that all EEF1A2 mutations were associated with epilepsy and intellectual disability, suggesting its critical role in neurodevelopment. Missense mutations with severe molecular alteration in the t-RNA binding sites or GTP hydrolysis domain were associated with early-onset severe epilepsy, indicating that the clinical expression was potentially determined by the location of mutations and alteration of molecular effects. This study highlights the potential genotype-phenotype relationship in EEF1A2 and facilitates the evaluation of the pathogenicity of EEF1A2 mutations in clinical practice.

Spatiotemporal disturbances and attribution analysis of mangrove in southern China from 1986 to 2020 based on time-series Landsat imagery.

As one of the most productive ecosystems in the world, mangrove has a critical role to play in both the natural ecosystem and the human economic and social society. However, two thirds of the world's mangrove have been irreversibly damaged over the past 100 years, as a result of ongoing human activities and climate change. In this paper, adopting Landsat for the past 36 years as the data source, the detection of spatiotemporal changes of mangrove in southern China was carried out based on the Google Earth Engine (GEE) cloud platform using the LandTrendr algorithm. In addition, the attribution of mangrove disturbances was analyzed by a random forest algorithm. The results indicated the area of mangrove recovery (5174.64 hm2) was much larger than the area of mangrove disturbances (1625.40 hm2) over the 35-year period in the study area. The disturbances of mangrove in southern China were dominated by low and low-to-medium-level disturbances, with an area of 1009.89 hm2, accounting for 57.50 % of the total disturbances. The mangrove recovery was also dominated by low and low-to-medium-level recovery, with an area of 3239.19 hm2, accounting for 62.61 % of the total recovery area. Both human and natural factors interacted and influenced each other, together causing spatiotemporal disturbances of mangrove in southern China during 1986-2020. The mangrove disturbances in the Phase I (1986-2000) and Phase III (2011-2020) were characterized by human-induced (50.74 % and 58.86 %), such as construction of roads and aquaculture ponds. The mangrove disturbances in the Phase II (2001-2010) were dominated by natural factors (55.73 %), such as tides, flooding, and species invasions. It was also observed that the area of mangrove recovery in southern China increased dramatically from 1986 to 2020 due to the promulgation and implementation of the Chinese government's policy on mangrove protection, as well as increased human awareness of mangrove wetland protection.

Activities of BiFeO3/carbon-dots catalysts in piezo-photocatalytic degradation of ciprofloxacin upon light/ultrasonic excitation.

Designing catalysts that can effectively make use of renewable energy benefits to solve the current challenges of environmental pollution and increasing energy demands. Piezo-photocatalysis that can utilize solar energy and natural vibration-energy has emerged as a "green" technique. In this work, we fabricated BiFeO3/C nano composites that can harvest solar and vibration energies and degrade organic pollutants. The incorporated carbon quantum dots bring about more efficient visible light absorbance and separation of photoinduced electron-hole pairs. The piezoelectric polarization further suppresses the recombination of photoinduced electron-hole pairs. The catalysts own higher reaction rates in piezo-photocatalysis and the BiFeO3/C-0.12 shows the highest degradation efficiency (k-value of 0.0835 min-1).

M6A "Writer" Gene METTL14: A Favorable Prognostic Biomarker and Correlated With Immune Infiltrates in Rectal Cancer.

Rectal cancer (RC) is the leading cause of tumor-related death among both men and women. The efficacy of immunotherapy for rectal cancer is closely related to the immune infiltration level. The N6-methyladenosine (m6A) modification may play a pivotal role in tumor-immune interactions. However, the roles of m6A-related genes in tumor-immune interactions of rectal cancer remain largely unknown. After an evaluation on the expression levels of m6A-related genes and their correlations with the prognosis of rectal cancer patients, we found that METTL14 was the only gene to be significantly correlated with prognosis in rectal cancer patients. Therefore, we further observed the impact of METTL14 expression and m6A modification on the immune infiltration in rectal cancer. Our study indicates that low expression of the m6A "writer" gene METTL14 in rectal cancer may lead to the downregulation of m6A RNA modification, thus reducing the level of immune cell infiltration and resulting in poor prognosis. METTL14 expression level is an independent prognostic factor in rectal cancer and is positively correlated with the immune infiltration level. Our study identified METTL14 as a potential target for enhancing immunotherapy efficacy in rectal cancer.

MLH1 Deficiency Induces Cetuximab Resistance in Colon Cancer via Her-2/PI3K/AKT Signaling.

The rapid onset of resistance to cetuximab (CTX) limits its clinical utility in colorectal cancer (CRC) patients. This study aims to understand a potential role of mismatch repair gene mutL homolog 1 (MLH1) in CTX response. Functional analysis of MLH1 in Her-2/phosphoinositide 3-kinases (PI3K)/PKB protein kinase (AKT)-regulated CTX sensitivity is performed using human CRC specimens, CRC cell lines with different MLH1 expression levels, and a subcutaneous xenograft model. Overexpression, knockdown, small interfering RNA, and inhibitors are used to examine the role of MLH1 and HER-2 downstream signaling and apoptotic targets in CTX sensitivity. Reduced MLH1 expression is correlated with unfavorable prognosis in cetuximab-treated patients. MLH1 loss decreases CTX sensitivity through Her-2/PI3K/AKT signaling and apoptosis resistance in culture and in xenografts, while MLH1 overexpression increases CTX sensitivity. Blocking Her-2 signaling increases CTX sensitivity of microsatellite instability CRC in vitro and in vivo. MLH1 loss induces activation of Her-2/PI3K/AKT signaling and leads to cetuximab resistance in colon cancer.

Study on the Clinical Features of Parkinson's Disease With Probable Rapid Eye Movement Sleep Behavior Disorder.

Objective: To investigate the clinical features and factors associated with Parkinson's disease (PD) patients with probable rapid eye movement sleep behavior disorder (PD-pRBD). Methods: A total of 2,440 patients with clinically established or clinically probable PD were divided into two groups: PD-pRBD and PD without pRBD (PD-NRBD), according to the RBD questionnaire-Hong Kong. Data collection included demographic data, basic clinical history, and motor and non-motor symptoms. Based on the onset time of pRBD and the motor symptoms in PD, PD-pRBD patients were further divided into the pRBD prior to PD (PD-prRBD) group and the pRBD posterior to PD (PD-poRBD) group. Clinical features were compared between the PD-pRBD and PD-NRBD groups, as well as the PD-prRBD and PD-poRBD groups. The associated factors of pRBD were also explored. Results: The prevalence of pRBD was 41.4% (1,010 out of the total of 2,440) in our PD cohort. Further, compared with the PD-NRBD group, the PD-pRBD group had longer disease duration and more severe motor symptoms. Moreover, the PD-pRBD group had significantly higher levodopa equivalent daily dose and a higher ratio of dyskinesia, wearing-off, and offset of the Hoehn-Yahr stage. The scores on the non-motor symptom rating scale (NMSS), cognitive impairment, Parkinson's disease sleep scale (PDSS), excessive daytime sleepiness, constipation, hyposmia, depression, and the 39-item Parkinson's disease questionnaire also appeared worse in the PD-pRBD group. Significant differences in the educational level, disease duration, disease progression, Unified Parkinson's Disease Rating Scale (UPDRS)-II, UPDRS-III, tremor, rigidity, bradykinesia, posture gait, frozen gait, levodopa equivalent daily dose, dyskinesia, wearing-off, Hoehn-Yahr stage, NMSS-6, PDSS, and communication score widely existed between the PD-prRBD and PD-poRBD groups. Late-onset PD, long disease duration, high UPDRS-I score, high NMSS-4 score, low PDSS score, constipation, and hyposmia were all identified as the risk factors for PD-pRBD. Conclusions: Compared with the PD-NRBD group, the PD-pRBD group may have more severe motor symptoms, motor complications, and non-motor symptoms as well as a substandard quality of life. Further, late-onset PD, long disease duration, high UPDRS-I score, high NMSS-4 score, low PDSS score, constipation, and hyposmia can be risk factors for RBD in PD. Differences also occurred between the PD-prRBD and PD-poRBD groups.