Construction and validation of a bioinformatics­based screen for cuproptosis­related genes and risk model for Alzheimer's disease.

The present study aimed to validate the association between core cuproptosis genes (CRGs) and Alzheimer's disease (AD) from both bioinformatics and experimental perspectives and also to develop a risk prediction model. To this end, 78 human­derived temporal back samples were analyzed from GSE109887, and the biological functions of the resulting CRGs were explored by cluster analysis, weighted gene co­expression network analysis and similar methods to identify the best machine model. Moreover, an external dataset GSE33000 and a nomogram were used to validate the model. The mRNA and protein expression of CRGs were validated using the SH­SY5Y cell model and the Sprague­Dawley rat animal model. The RT­qPCR and western blotting results showed that the mRNA and protein expression content of dihydrolipoamide dehydrogenase, ferredoxin 1, glutaminase and pyruvate dehydrogenase E1 subunit ß decreased, and the expression of dihydrolipoamide branched chain transacylase E2 increased in AD, which supported the bioinformatic analysis results. The CRG expression alterations affected the aggregation and infiltration of certain immune cells. The present study also confirmed the accuracy and validity of AD diagnostic models and nomograms, and validated the association between five CRGs and AD, indicating a significant difference between patients with AD and healthy individuals. Therefore, CRGs are expected to serve as relevant biomarkers for the diagnosis and prognostic monitoring of AD.

Head-to-head comparison of [68Ga]Ga-FAPI PET and [18F]FDG PET in the detection of bone and lymph node metastasis in various cancers: A systematic review and meta-analysis.

PURPOSE: The aim of our meta-analysis and systematic review was to contrast the positivity rates of [68Ga]Ga-FAPI PET and [18F]FDG PET in detecting bone and lymph node metastases across diverse cancer types. METHODS: We conducted a comprehensive search for eligible articles up until August 2023, utilizing databases including PubMed, Embase, and Web of Science. Studies focusing on the positivity rate of [68Ga]Ga-FAPI PET vs. [18F]FDG PET for bone and lymph metastasis were included. Using random-effect model, the positivity rate for [68Ga]Ga-FAPI PET and [18F]FDG PET were generated. In order to gauge the heterogeneity among aggregated studies, we utilized the I2 statistic. Additionally, we applied the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) methodology to evaluate the caliber of the studies encompassed in our analysis. RESULTS: A total of 430 publications were initially identified in the search. Eventually, 25 studies, involving 779 patients, met the inclusion criteria. In terms of bone metastasis, the findings indicate no statistically significant difference between the use of [68Ga]Ga-FAPI PET and [18F]FDG PET (P = 0.34). However, concerning lymph node metastasis, the results demonstrate significant difference between the two imaging agents (P = 0.04). CONCLUSIONS: This systematic review suggests that [68Ga]Ga-FAPI PET appears to outperform [18F]FDG PET in detecting lymph node metastases. However, when it comes to bone metastasis, no statistically significant difference was observed. It is crucial to acknowledge that the insights concerning bone metastasis stem from studies with comparatively modest sample sizes. Consequently, there is a pressing demand for further, expansive prospective studies in this field.

[Comparative study of femoral head replacement and internal fixation in the treatment of unstable intertrochanteric fractures in the elderly].

OBJECTIVE: To compare the clinical efficacy of femoral head replacement and internal fixation in the treatment of unstable intertrochanteric fractures in the elderly. METHODS: Retrospective analysis of 70 cases of unstable intertrochanteric fractures treated from January 2016 to January 2019 and meeting the inclusion and exclusion criteria, 39 cases were fixed with closed reduction and new proximal femoral intramedullary nail(InterTAN), and 31 cases were treated with open trochanter reconstruction and artificial femoral head replacement. The operation time, intraoperative bleeding, hospital stay, weight bearing time, postoperative complication rate and hip function recovery (Harris score) were compared between two groups. RESULTS: All cases were followed up for 12 to 24 months. There were no significant differences in intraoperative bleeding and hospital stay between the two groups (P>0.05). The operation time in replacement group was longer than that in internal fixation group (P< 0.05). The postoperative weight-bearing time in replacement group was significantly earlier than that in internal fixation group (P<0.05). In the replacement group, there were 1 case of pulmonary infection, 1 case of deep venous thrombosis and 1 case of periprosthetic fracture;in the internal fixation group, there were 4 cases of pulmonary infection, 3 cases of internal fixation failure, 3 cases of cerebral infarction and 2 cases of urinary infection;there was significant difference between two groups (P< 0.05). The Harris score in replacement group was higher than that in internal fixation group one month after operation (P< 0.05), but there was no significant difference between two groups at 12 months after operation(P>0.05). CONCLUSION: InterTAN and femoral head replacement can treat unstable intertrochanteric fractures in the elderly, but femoral head replacement can move down early, improve the quality of life at the end of life, reduce postoperative complications and facilitate the treatment of coexisting diseases in internal medicine.

Hidden species diversity in Pachyhynobius: A multiple approaches species delimitation with mitogenomes.

The lack of distinct morphological features of cryptic species is a hard problem for taxonomy, especially when the taxa are closely related with considerable amounts of ancestral polymorphism. Lately, intensive coalescent-based analyses involving multiple loci have become the preferred method to assess the extent of genetic distinctiveness in otherwise phenotypically similar populations. Previously, phylogenetic studies on Pachyhynobius shangchengensis uncovered five extremely deeply divergent clades, which suggested that this species may be a cryptic species complex. In this study, we used the complete mitochondrial genome data and samples from the entire range of stout salamander (Pachyhynobius), as well as publicly available mitochondrial genomes to assess species boundaries within this genus using a suite of diverse methodologies (e.g. general mixed Yule coalescent model, Automatic Barcode Gap Discovery). The phylogenetic relationships recovered two major groups within P. shangchengensis, with one group formed by four of the six extant populations and corresponding to the central and eastern range of the Dabie mountains, while the other group encompassed two other lineages in the north west of the Dabie mountain range. The species delimitation comparison within Pachyhynobius supported the presence of recognized species within the genus, and consensus was observed across methods for the existence of up to five cryptic species within what has been traditionally considered to be P. shangchengensis. While this implies the existence of four taxa in addition to the described P. shangchengensis species, morphological data and life history information are further required to contribute to the species definition. The observed pattern of genetic variation is likely the outcome of a discontinuous habitat combined with niche conservatism, which produced the sky-island effect observed in Pachyhynobius, and which led to formation of a hidden species diversity in this genus.

Long-term sky islands generate highly divergent lineages of a narrowly distributed stream salamander (Pachyhynobius shangchengensis) in mid-latitude mountains of East Asia.

BACKGROUND: Climate oscillation may have a profound effect on species distributions, gene flow patterns and population demography. In response to environmental change, those species restricted to montane habitats experienced expansions and contractions along elevation gradients, which can drive differentiation among sky islands. RESULTS: The Shangcheng stout salamander (Pachyhynobius shangchengensis) is a cool stream amphibian restricted to high-elevation areas in the Dabie Mountains, East China. In the present study, we used mtDNA genes (Cyt b and ND2) of 193 individuals and 12 nuclear microsatellite loci genotyped on 370 individuals, representing 6 populations (JTX, KHJ, MW, TTZ, BYM and KJY) across the taxon's distribution area, to investigate their genetic variation and evolutionary history of P. shangchengensis. Most populations showed unusually high levels of genetic diversity. Phylogenetic analyses revealed five monophyletic clades with divergence times ranging from 3.96 to 1.4 Mya. Accordingly, significant genetic differentiation was present between these populations. Bayesian skyline plot analyses provided that all populations underwent long-term population expansions since the last inter-glacial (0.13 Mya ~ 0.12 Mya). Msvar analyses found recent signals of population decline for two northern populations (JTX and KHJ) reflecting a strong bottleneck (approximately 15-fold decrease) during the mid-Holocene (about 6000 years ago). Ecological niche modelling has shown a discontinuity in suitable habitats for P. shangchengensis under different historical climatic conditions. CONCLUSIONS: Our results suggest that the niche conservatism of P. shangchengensis and sky island effects may have led to long-term isolation between populations. In sky island refuges, the mid-latitude Dabie Mountains have provided a long-term stable environment for P. shangchengensis, which has led to the accumulation of genetic diversity and has promoted genetic divergence.

The complete mitochondrial genome of Tylototriton anhuiensis and implications for its taxonomy.

Tylototriton anhuiensis (Salamandridae, Urodela), collected from Yaoluoping Nature Reserve, was identified as a new species. The complete mitogenome sequence of T. anhuiensis is 16,259 by in length, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and D-loop region. The base composition of the mitogenome was 33.6%A, 26.3% C, 14.5% G, and 25.6% T. The ND6 subunit gene and eight tRNA genes were encoded on the L-strand, the others were encoded on the H-strand.