Search

While shifts in gut microbiota have been studied in diseased states, the temporal variability of the microbiome in cats has not been widely studied. This study investigated the temporal variability of the feline dysbiosis index (DI) and the abundance of core bacterial groups in healthy adult cats. The secondary aim was to evaluate the relationship between the fecal abundance of Clostridium hiranonis and the fecal concentrations of unconjugated bile acids. A total of 142 fecal samples collected from 17 healthy cats were prospectively included: nine cats with weekly collection over 3 weeks (at least four time points), five cats with monthly collection over 2 months (three time points), and three cats with additional collections for up to 10 months. The DI remained stable within the reference intervals over two months for all cats (Friedman test, p > 0.2), and 100% of the DI values (n = 142) collected throughout the study period remained within the RI. While some temporal individual variation was observed for individual taxa, the magnitude was minimal compared to cats with chronic enteropathy and antibiotic exposure. Additionally, the abundance of Clostridium hiranonis was significantly correlated with the percentage of fecal primary bile acids, supporting its role as a bile acid converter in cats.

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed subgenome dominance remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

Metastable beta titanium alloys (Ti-5Mo-xFe) were designed for biomedical applications with high strength and high cycle fatigue properties in this study. By varying Fe content (1, 2, and 4 wt%), we assessed changes in phase composition, grain refinement, and intermetallic compound formation to optimize the alloy for biomedical applications. The results revealed that increased Fe content enhances hardness and yield strength due to solid solution strengthening and grain refinement but slightly decreases corrosion resistance. Additionally, the microstructural evolution affected fatigue properties, with the basket-weave structure in Ti-5Mo-1Fe improving crack resistance, while the lamellar structures in higher Fe alloys exhibited lower fatigue resistance. These findings highlight the potential of Ti-5Mo-xFe alloys as cost-effective high-performance materials for implants, contributing to the tailored mechanical and electrochemical properties essential for biomedical applications.

Abstract In this paper, we study the existence of multiple solutions for the following nonlinear elliptic problem of p-Laplacian type involving a singularity and a critical Sobolev exponent { − Δ p u = u p ∗ − 1 + λ | u | γ − 1 u , in Ω , u = 0 , on ∂ Ω , $$ \textstyle\begin{cases} -\Delta _{p}u=u^{p^{*}-1}+\frac{\lambda}{|u|^{\gamma -1}u}, & \text{in} ~\Omega , \\ u=0, &\text{on}~\partial \Omega , \end{cases} $$ where Ω is a bounded domain, p ∗ = N p N − p $p^{\ast}=\frac{Np}{N-p}$ ( N ≥ 3 $N \geq 3$ ) is the critical Sobolev exponent and λ > 0 $\lambda > 0$ . Based on the cutoff technique, we prove that the above problem possesses infinitely many positive solutions with 0 < γ < 1 , 1 < p < N $0 < \gamma 0 $\lambda > 0$ small enough.

Abstract Thioflavin-T (THT) is a common and indispensable tool for the study of amyloid pathologies and protein aggregation, both in vitro and for histological samples. In this study we expand the use of THT beyond its canonical usage for staining amyloid plaques and demonstrate its novel use as an easy and rapid stain comparable to fluorescent Nissl staining, allowing for clear discernment of neuronal cell bodies and also nucleoli in fixed tissue and live cells. We believe that this is of value for any lab that studies central nervous system (CNS) tissues. Furthermore, we show that THT could potentially be used as a an alternative to the use of fluorescent reporters or other more costly RNA binding compounds in the study of nucleolar dynamics owing to its ability to clearly stain nucleoli in live cells. We also discovered the previously unreported effect of blue light exposure on the photo enhancement of THT excited by a 488 nm laser in stained tissue sample and how to avoid complications arising from this effect. Finally, we provide a simple protocol that can be easily adjusted either for using THT as a neuronal cell body and nucleoli stain, compatible with antibody based staining methods tested up to 4 fluorophores, or alternatively by using an additional washing step the protocol may be used for amyloid plaque detection in fixed brain tissue.

Abstract Diffusion-weighted magnetic resonance imaging (DW-MRI) performed before target temperature management, within 6 h of return of spontaneous circulation (ROSC), is defined as ultra-early DW-MRI. In previous studies, high-signal intensity (HSI) on ultra-early DW-MRI can predict poor neurological outcomes (Cerebral Performance Category 3–5 at 6-months post-ROSC). We aimed to assess the optimal-timing for ultra-early DW-MRI to avoid false-negative outcomes post out-of-hospital cardiac arrest, considering cardiopulmonary resuscitation (CPR) factors. The primary outcomes were HSI in the cerebral cortex or deep gray matter on ultra-early DW-MRI. The impact of CPR factors and ROSC to DW-MRI scan-interval on HSI-presence was assessed. Of 206 included patients, 108 exhibited HSI-presence, exclusively associated with poor neurological outcomes. In multivariate regression analysis, ROSC to DW-MRI scan-interval (adjusted odds ratio [aOR], 1.509; 95% confidence interval (CI): 1.113–2.046; P = 0.008), low-flow time (aOR, 1.176; 95%CI: 1.121–1.233; P

Abstract We evaluated alterations in cerebrospinal fluid (CSF) flow based on the neurological prognosis of out-of-hospital cardiac arrest (OHCA) patients. This prospective observational study was conducted from May 2023 to June 2024. Stroke distance was measured using magnetic resonance imaging flowmetry immediately and at 72 h after return of spontaneous circulation (ROSC), with negative values indicating caudocranial direction. The caudocranial direction of CSF flow was observed in 17 (56.7%) patients immediately after ROSC, and in 20 (66.7%) patients at 72 h after ROSC. There was no significant difference in the occurrence of caudocranial CSF flow immediately after ROSC between the groups with good and poor neurological prognosis [6 (50.0%) vs. 11 (61.1%); p = 0.55]. However, the occurrence of caudocranial CSF flow at 72 h after ROSC was significantly higher in the group with poor neurological prognosis compared to the group with good neurological prognosis [3 (25.0%) vs. 17 (94.4%); p

The genus Albatrellus is an important group of stipitate terrestrial fungi in the order Russulales. Some species in the genus form ectomycorrhizae, mostly with trees of Pinaceae; some are well-known edible mushrooms. However, its diversity and biogeography are unclear. Taxonomic and phylogenetic studies on Albatrellus were carried out by morphological examination, which included detailed observations of the fruiting body, spore shape and size, and other key features, together with potential hosts. These observations were then compared and analysed using multi-locus molecular phylogenetic analyses, including the internal transcribed spacer regions (ITS), the large subunit nuclear ribosomal RNA gene (nLSU), the translation elongation factor 1-α gene (tef1), the largest subunit of RNA polymerase II (rpb1), the second largest subunit of RNA polymerase II (rpb2), the small subunit mitochondrial rRNA gene (mtSSU), and the small subunit of the nuclear ribosomal RNA gene (nucSSU). The results demonstrated that the species of Albatrellus formed eight clades. Nine new species are described and illustrated, and two new combinations are proposed. A total of 38 species are accepted in Albatrellus worldwide. Of those species, 26, 7, and 8 species are distributed in Asia, Europe, and North America, respectively. The divergence time indicated that the maximum crown age of Albatrellus was approximately 70.5 million years ago, and East Asia and North America are the likely ancestral areas. Dispersal and differentiation to other continents occurred during the late Paleocene and Miocene. Three kinds of dispersal routes are proposed: East Asia and Europe, East Asia and North America, and Europe and North America.

Abstract Background Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China. Methods A total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018–2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis. Results A shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January–April and October–December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P

Abstract Background Loss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype–phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells. Methods We used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms. Results Zbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. Conclusions Zbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.

Acetaminophen (APAP) overdose can induce hepatocyte necrosis and acute liver failure in experimental rodents and humans. APAP is mainly metabolized via hepatic cytochrome P450 enzymes to generate the highly reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which forms acetaminophen protein adducts (APAP-adducts) and damages mitochondria, triggering necrosis. APAP-adducts and damaged mitochondria can be selectively removed by autophagy. Increasing evidence implies that the activation of autophagy may be beneficial for APAP-induced liver injury (AILI). In this minireview, we briefly summarize recent progress on autophagy, in particular, the pharmacological targeting of SQSTM1/p62 and TFEB in AILI.

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) is a promising therapeutic target for cancer therapy. In this work, we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors, leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent, selective, orally bioavailable allosteric SHP2 inhibitor (SHP2WT IC50 = 2.7 nmol/L) with favorable pharmacokinetic profiles (F = 42.5%; t1/2 = 2.47 h). Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the “tunnel” allosteric site of SHP2. TK-642 could effectively suppress cell proliferation (KYSE-520 cells IC50 = 5.73 μmol/L) and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling pathways. Additionally, oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model, with a T/C value of 83.69%. Collectively, TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

Abstract Background No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment. Methods This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26). Results Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p

Abstract Flying ad hoc network (FANET) is a new technology, which creates a self-organized wireless network containing unmanned aerial vehicles (UAVs). In FANET, routing protocols deal with important challenges due to limited energy, frequent link failures, high mobility of UAVs, and limited communication range of UAVs. Thus, a suitable path is always essential to transmit data between UAVs. In this paper, a local filtering-based energy-aware routing scheme (LFEAR) is proposed for FANETs. LFEAR improves the template of the route request (RREQ) packet by adding three fields, namely the energy, reliable distance, and movement similarity of the relevant route to create stable and energy-efficient paths. In the routing process, LFEAR presents a local filtering construction technique to avoid the broadcasting storm issue. This filter limits the broadcasting range of RREQs in the network. Accordingly, only UAVs inside this local filtered area can rebroadcast RREQs and other UAVs must eliminate these packets. After ending the route discovery process, the destination begins the route selection phase and extracts information about each discovered route, including the number of hops, route energy, reliable distance, and movement similarity. Then, the destination node calculates a score for each path based on the extracted information, selects the route with the highest score, and sends a route reply (RREP) packet to the source node through this route. Finally, the simulation process of LFEAR is performed using the NS2 simulator, and two simulation scenarios, namely change in network density and change in the speed of UAVs, are defined to evaluate network performance. In the first scenario, LFEAR improves energy consumption, packet delivery rate, network lifespan, and delay by 1.33%, 1.77%, 6.74%, and 1.71%, while its routing overhead is about 16.51% more than EARVRT. In the second scenario, LFEAR optimizes energy consumption and network lifetime by 5.55% and 5.67%, respectively. However, its performance in terms of routing overhead, packet delivery rate, and delay is 23%, 2.29%, and 6.67% weaker than EARVRT, respectively.

Two taxonomically controversial polypore genera with reddish brown to orange basidiomata that stain reddish with KOH solution, Aurantiporus and Hapalopilus, are revised based on additional sampling, morphological examination, and phylogenetic analysis of a combined dataset of ITS1-5.8S-ITS2-nLSU sequences. Hapalopilus is a monophyletic genus belonging to Phanerochaetaceae, whereas Aurantiporus is a polyphyletic genus belonging to Meruliaceae. Hapalopilus and Aurantiporus s. str. are circumscribed, and two new species – Aurantiporus orientalis and Hapalopilus tabuliformis – are described and illustrated from temperate China. In addition, four new combinations, viz. Aurantiporus alboaurantius, A. mutans, A. tropicus and Luteoporia albocitrina, are proposed based on morphology and phylogenetic analysis. The relationships between Aurantiporus and Hapalopilus are discussed.

Abstract Background Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is a rare inherited metabolic disease caused by the mutation in the CYP27A1 gene. Spinal CTX is a rare clinical subgroup of CTX which lacks typical symptoms seen in classical CTX. Here we report a spinal CTX case revealed double mutation of CYP27A1 gene. Case presentation A 42-year-old Asian man visited our hospital with spastic gait started at 35. Physical examination showed bilateral masses on his Achilles tendons and were identified as xanthoma on ankle magnetic resonance imaging (MRI). Brain and spinal cord MRI revealed high signal lesions in bilateral cerebellar dentate nuclei and long tract lesions involving lateral corticospinal and gracile tracts. Gene analysis revealed double heterozygous mutation, c.223C > T (p. Gln75Ter) and c.1214G > A (p. Arg405Gln). Conclusions We believe that novel mutation detected in our case might have a role in the pathomechanism in CTX. Moreover, spinal CTX should be considered in the patients only presenting with pyramidal symptoms, as CTX shows good prognosis in early treatment with chenodeoxycholic acid.

Four new fungi from Xizang in southwest China, Calocera ramaria, Ceraceomyces rhizomorphus, Leptosporomyces linzhiensis, and Ramaria xizangensis are described and illustrated based on the morphological and molecular evidence. Calocera ramaria is characterized by the ramal and bright orange basidiomata, a monomitic hyphal system with simple septa generative hyphae, usually 4-septate basidiospores; Ceraceomyces rhizomorphus is characterized by the cream to yellowish basidiomata with rhizomorphs, cylindrical basidiospores; Leptosporomyces linzhiensis is characterized by white with pink basidiomata, cylindrical to oblong ellipsoid basidiospores; Ramaria xizangensis is characterized by flesh pink basidiomata, branched dichotomously in 4–5 ranks, a monomitic hyphal system with clamped generative hyphae, ellipsoid to cylindrical and densely warted basidiospores.

Abstract When implementing optoelectronic devices through the stacking of heterogeneous materials, considering the bandgap offset is crucial for achieving efficient carrier dynamics. In this study, the bandgap offset characteristics are investigated when n‐type gallium nitride nanowires (n‐GaN NWs) are used as electron transport layers in methylammonium lead iodide (MAPbI3)‐based optoelectronic devices. n‐GaN NWs are grown on indium‐tin‐oxide (ITO)‐coated glass via the plasma‐assisted molecular beam epitaxy (PA‐MBE) process to form the “GaN NWs‐on‐glass” platform. A MAPbI3 thin film is then spin‐coated on the GaN NWs‐on‐glass. X‐ray photoelectron spectroscopy (XPS) shows that the valence and conduction band offsets in the MAPbI3/n‐GaN heterostructure are 2.19 and 0.40 eV, respectively, indicating a type‐II band alignment ideal for optoelectronic applications. Prototype photovoltaic devices stacking perovskite on GaN NWs‐on‐glass show excellent interfacial charge‐transfer ability, photon recycling, and carrier extraction efficiency. As a pioneering step in exploiting the diverse potential of the GaN‐on‐glass, it is demonstrated that the junction characteristics of MAPbI3/n‐GaN NW heterostructures can lead to a variety of optoelectronic device applications.

Microbes have been suspected to cause Alzheimer’s disease since at least 1908, but this has generally remained unpopular in comparison to the amyloid hypothesis and the dominance of Aβ and Tau. However, evidence has been accumulating to suggest that these earlier theories are but a manifestation of a common cause that can trigger and interact with all the major molecular players recognized in AD. Aβ, Tau and ApoE, in particular appear to be molecules with normal homeostatic functions but also with alternative antimicrobial functions. Their alternative functions confer the non-immune specialized neuron with some innate intracellular defenses that appear to be re-appropriated from their normal functions in times of need. Indeed, signs of infection of the neurons by biofilm-forming microbial colonies, in synergy with herpes viruses, are evident from the clinical and preclinical studies we discuss. Furthermore, we attempt to provide a mechanistic understanding of the AD landscape by discussing the antimicrobial effect of Aβ, Tau and ApoE and Lactoferrin in AD, and a possible mechanistic link with deficiency of vital copper-based systems. In particular, we focus on mitochondrial oxidative respiration via complex 4 and ceruloplasmin for iron homeostasis, and how this is similar and possibly central to neurodegenerative diseases in general. In the case of AD, we provide evidence for the microbial Alzheimer’s disease (MAD) theory, namely that AD could in fact be caused by a long-term microbial exposure or even long-term infection of the neurons themselves that results in a costly prolonged antimicrobial response that disrupts copper-based systems that govern neurotransmission, iron homeostasis and respiration. Finally, we discuss potential treatment modalities based on this holistic understanding of AD that incorporates the many separate and seemingly conflicting theories. If the MAD theory is correct, then the reduction of microbial exposure through use of broad antimicrobial and anti-inflammatory treatments could potentially alleviate AD although this requires further clinical investigation.