Ancient Mitochondrial Genomes Provide New Clues in the History of the Akhal-Teke Horse in China.

This study analyzed ancient DNA from the remains of horses unearthed from the Shihuyao tombs. These were found to date from the Han and Tang Dynasties in Xinjiang (approximately 2200 to 1100 years ago). Two high-quality mitochondrial genomes were acquired and analyzed using next-generation sequencing. The genomes were split into two maternal haplogroups, B and D, according to a study that included ancient and contemporary samples from Eurasia. A close genetic affinity was observed between the horse of the Tang Dynasty and Akhal-Teke horses according to the primitive horse haplotype G1. Historical evidence suggests that the ancient Silk Road had a vital role in their dissemination. Additionally, the matrilineal history of the Akhal-Teke horse was accessed and suggested that the early domestication of the breed was for military purposes.

Establishment of a Predictive Model for Acute Respiratory Distress Syndrome in Patients with Bacterial Pneumonia.

Background: Community-acquired pneumonia (CAP) is a global health concern due to its high rates of morbidity and mortality. Bacterial pathogens are common causes of CAP. It is one of the most common causes of acute respiratory distress syndrome (ARDS), a common severe respiratory system manifestation threatening human health. This study aimed to establish a predictive model for ARDS in patients with bacterial pneumonia, which was conducive to early identification of the occurrence and effective prevention of ARDS. Methods: We collected the clinical data of hospitalized patients with bacterial pneumonia in Affiliated Huzhou Hospital of Zhejiang University School of Medicine from January 2022 to November 2022. The independent risk factors for ARDS in patients with bacterial pneumonia were determined by univariate and multivariate binary logistic regression analyses. The nomogram was constructed to display the predictive model, and the receiver-operating characteristic curve was plotted to evaluate the predictive value of ARDS. Results: This study included 254 patients with bacterial pneumonia, of which 114 developed ARDS. The multivariate logistic regression analysis revealed age [odds ratio (OR) = 1.041, P = 0.003], heart rate (OR = 1.020, P = 0.028), lymphocyte count (OR = 0.555, P = 0.033), white blood cell count (OR = 1.062, P = 0.033), bilateral lung lesions (OR = 7.352, P = 0.011) and pleural effusion (OR = 2.512, P = 0.002) as the independent risk factors for ARDS. The predictive model was constructed based on the six independent factors, which was valuable in predicting ARDS with area under the curve of 0.794. Conclusion: The predictive model was beneficial to evaluate the disease progression in patients with bacterial pneumonia and identify ARDS. Further, our nomogram might help doctors predict the incidence of ARDS and conduct treatment as early as possible.

Quantum dots-based multiplexed immunosensors for accurate diagnosis of attention deficit hyperactivity disorder in childhood.

Attention-deficit/hyperactivity disorder (ADHD) lacks objective diagnostic markers. In clinical settings, reliance on subjective judgments can often lead to missed or misdiagnoses. Some biomarkers have been reported to be associated with ADHD, but using one biomarker alone is not enough. To address this, we developed a fluorescent immunoassay platform based on quantum dots (QDs) to detect assay capable of detecting and quantifying multiple biomarkers simultaneously. Specifically, we were able to the simultaneously detect brain-derived neurotrophic factor, tumor necrosis factor-alpha, interleukin-6 and ferritin using different emission spectra QDs. The QD-based multiplexed immunoassay displayed a low detection of limit in the range of 0.021-0.068 pg/mL, and the assay showed satisfactory reproducibility and precision. We then quantified all four targets from ADHD patient's plasma samples, where it showed remarkable consistency with clinical test for ADHD diagnosis. This methodological comparison supports the diagnosis of ADHD using our assay.

Biomimetic nano-chelate diethyldithiocarbamate Cu/Fe for enhanced metalloimmunity and ferroptosis activation in glioma therapy.

Ferroptosis has emerged as a promising therapeutic approach for glioma. However, its efficacy is often compromised by the activated GPX4-reduced glutathione (GSH) system and the poor brain delivery efficiency of ferroptosis inducers. Therefore, suppression of the GPX4-GSH axis to induce the accumulation of lipid peroxides becomes an essential strategy to augment ferroptosis. In this study, we present a metalloimmunological strategy to target the GPX4-GSH axis by inhibiting the cystine/glutamate antiporter system (system Xc-) and glutathione synthesis. To achieve this, we developed a complex of diethyldithiocarbamate (DDC) chelated with copper and ferrous ions (DDC/Cu-Fe) to trigger T-cell immune responses in the tumor microenvironment, as well as to inhibit tumor-associated macrophages, thereby alleviating immunosuppression. To enhance brain delivery, the DDC/Cu-Fe complex was encapsulated into a hybrid albumin and lactoferrin nanoparticle (Alb/LF NP), targeting the nutrient transporters (e.g., LRP-1 and SPARC) overexpressed in the blood-brain barrier (BBB) and glioma cells. The Alb/LF NP effectively promoted the brain accumulation of DDC/Cu-Fe, synergistically induced ferroptosis in glioma cells and activated anticancer immunity, thereby prolonging the survival of glioma-bearing mice. The nanoformulation of DDC/Cu-Fe provides a promising strategy that combines ferroptosis and metalloimmunology for glioma treatment.

Blocking tumor-platelet crosstalk to prevent tumor metastasis via reprograming glycolysis using biomimetic membrane-hybridized liposomes.

Activated platelets promote tumor progression and metastasis through active interactions with cancer cells, especially in promoting epithelial-mesenchymal transition (EMT) of tumor cells and shedding tumor cells into the blood. Blocking platelet-tumor cell interactions can be a potential strategy to inhibit tumor metastasis. Platelet activation requires energy produced from aerobic glycolysis. Based on this, we propose a platelet suppression strategy by reprogramming glucose metabolism of platelets, which has an advantage over conventional antiplatelet treatment that has a risk of serious hemorrhage. We develop a biomimetic delivery system using platelet membrane-hybridized liposomes (PM-Lipo) for codelivery of quercetin and shikonin to simultaneously inhibit lactate transporter MCT-4 and a glycolytic enzyme PKM2 for achieving metabolic reprogramming of platelets and suppressing platelet activation. Notably, PM-Lipo can also inhibit glycolysis in cancer cells, which actually takes "two-birds-one-stone" action. Consequently, the platelet-tumor cell interactions are inhibited. Moreover, PM-Lipo can bind with circulating tumor cells and reduce their seeding in the premetastatic microenvironment. The in vivo studies further demonstrated that PM-Lipo can effectively suppress primary tumor growth and reduce lung metastasis without affecting inherited functions of platelets. Reprogramming glycolysis of platelets can remodel the tumor immune microenvironment, including suppression of Treg and stimulation of CTLs.

Liposomal Resveratrol Alleviates Platelet Storage Lesion via Antioxidation and the Physical Buffering Effect.

Platelet transfusion is essential in the treatment of platelet-related diseases and the prevention of bleeding in patients with surgical procedures. Platelet transfusion efficacy and shelf life are limited mainly by the development of platelet storage lesion (PSL). Mitigating PSL is the key to prolonging the platelet shelf life and reducing wastage. Excess intracellular reactive oxygen species (ROS) are one of the main factors causing PSL. In this study, we explored a nanomedicine strategy to improve the quality and functions of platelets in storage. Resveratrol (Res), a natural plant product, is known for its antioxidative effect. However, medical applications of Res are limited due to its low water solubility and stability. Therefore, we used a resveratrol-loaded liposomal system (Res-Lipo) to better utilize the antioxidant effect of the drug. This study aimed to evaluate the effect of Res-Lipo on platelet oxidative stress and alleviation of PSL during the storage time. Res-Lipo scavenged intracellular ROS and inhibited platelet apoptosis and activation during storage. Res-Lipo not only maintained mitochondrial function but also improved platelet aggregation in response to adenosine 5'-diphosphate. These results revealed that Res-Lipo ameliorated PSL and prolonged the platelet survival time in vivo. The strategy provides a potential method for extending the platelet storage time and might be considered a potential and safe additive to alleviate PSL.

Ancient Mitochondrial Genomes Provide New Clues to the Origin of Domestic Cattle in China.

Cattle are one of the six livestock species that have occupied an important place in Chinese history. Previous ancient DNA studies have indicated that Chinese taurine cattle (Bos taurus taurus) are exotic, but the exact route and diffusion by which they were introduced to China is unknown. In this study, we extracted the mitochondrial genomes of 34 cases of ancient taurine cattle (from the late Neolithic to Qin and Han dynasties) excavated from sites in northern China and the eastern Eurasian steppe, and successfully obtained 14 mitochondrial genome sequences. The results of ancient DNA analysis reveal that with cultural exchange and trade, there was close genetic exchange between domestic taurine cattle in different regions. The haplotypes shared by domestic cattle have genetic continuity, reflecting the strong cultural influence of the large capital city sites such as Taosi, Shimao and Erlitou on the surrounding areas. This study suggests that ancient northern Chinese taurine cattle may have accompanied the westward transmission of agricultural or painted pottery culture and thus had a maternal genetic contribution to modern Tibetan cattle.

Progress on Physical Field-Regulated Micro/Nanomotors for Cardiovascular and Cerebrovascular Disease Treatment.

Cardiovascular and cerebrovascular diseases (CCVDs) are two major vasculature-related diseases that seriously affect public health worldwide, which can cause serious death and disability. Lack of targeting effect of the traditional CCVD treatment drugs may damage other tissues and organs, thus more specific methods are needed to solve this dilemma. Micro/nanomotors are new materials that can convert external energy into driving force for autonomous movement, which can not only enhance the penetration depth and retention rates, but also increase the contact areas with the lesion sites (such as thrombus and inflammation sites of blood vessels). Physical field-regulated micro/nanomotors using the physical energy sources with deep tissue penetration and controllable performance, such as magnetic field, light, and ultrasound, etc. are considered as the emerging patient-friendly and effective therapeutic tools to overcome the limitations of conventional CCVD treatments. Recent efforts have suggested that physical field-regulated micro/nanomotors on CCVD treatments could simultaneously provide efficient therapeutic effect and intelligent control. In this review, various physical field-driven micro/nanomotors are mainly introduced and their latest advances for CCVDs are highlighted. Last, the remaining challenges and future perspectives regarding the physical field-regulated micro/nanomotors for CCVD treatments are discussed and outlined.

Carrier-free nanoprodrug for p53-mutated tumor therapy via concurrent delivery of zinc-manganese dual ions and ROS.

Human cancers typically express a high level of tumor-promoting mutant p53 protein (Mutp53) with a minimal level of tumor-suppressing wild-type p53 protein (WTp53). In this regard, inducing Mutp53 degradation while activating WTp53 is a viable strategy for precise anti-tumor therapy. Herein, a new carrier-free nanoprodrug (i.e., Mn-ZnO2 nanoparticles) was developed for concurrent delivery of dual Zn-Mn ions and reactive oxygen species (ROS) within tumor to regulate the p53 protein for high anti-tumor efficacy. In response to the mild tumor acidic environment, the released Zn2+ and H2O2 from Mn-ZnO2 NPs induced ubiquitination-mediated proteasomal degradation of Mutp53, while the liberative Mn2+ and increased ROS level activated the ATM-p53-Bax pathway to elevate WTp53 level. Both in vitro and in vivo results demonstrated that pH-responsive decomposition of Mn-ZnO2 NPs could effectively elevate the intracellular dual Zn-Mn ions and ROS level and subsequently generate the cytotoxic hydroxyl radical (•OH) through the Fenton-like reaction. With the integration of multiple functions (i.e., carrier-free ion and ROS delivery, tumor accumulation, p53 protein modulation, toxic •OH generation, and pH-activated MRI contrast) in a single nanosystem, Mn-ZnO2 NPs demonstrate its superiority as a promising nanotherapeutics for p53-mutated tumor therapy.

Radiocarbon and genomic evidence for the survival of Equus Sussemionus until the late Holocene.

The exceptionally rich fossil record available for the equid family has provided textbook examples of macroevolutionary changes. Horses, asses, and zebras represent three extant subgenera of Equus lineage, while the Sussemionus subgenus is another remarkable Equus lineage ranging from North America to Ethiopia in the Pleistocene. We sequenced 26 archaeological specimens from Northern China in the Holocene that could be assigned morphologically and genetically to Equus ovodovi, a species representative of Sussemionus. We present the first high-quality complete genome of the Sussemionus lineage, which was sequenced to 13.4× depth of coverage. Radiocarbon dating demonstrates that this lineage survived until ~3500 years ago, despite continued demographic collapse during the Last Glacial Maximum and the great human expansion in East Asia. We also confirmed the Equus phylogenetic tree and found that Sussemionus diverged from the ancestor of non-caballine equids ~2.3-2.7 million years ago and possibly remained affected by secondary gene flow post-divergence. We found that the small genetic diversity, rather than enhanced inbreeding, limited the species' chances of survival. Our work adds to the growing literature illustrating how ancient DNA can inform on extinction dynamics and the long-term resilience of species surviving in cryptic population pockets.

Water-Soluble Polysaccharides Extracted from Pueraria lobata Delay Aging of Caenorhabditis elegans under Heat Stress.

Pueraria lobata is a perennial legume, commonly used as a food source in China. The polysaccharides extracted from P. lobata have demonstrated various biological activities. However their anti-aging effects and the underline mechanisms are largely unknown. In this study, water-soluble polysaccharides (WSPS) from P. lobata were extracted and demonstrated antioxidant activity against DPPH radicals and hydroxyl radicals in vitro. Using nematode Caenorhabditis elegans as a model, we found that WSPS remarkably prolonged the survival, increased growth and locomotion under heat stress. To investigate the possible mechanism, the levels of reactive oxygen species (ROS) and lipid peroxidation product malondialdehyde (MDA) were determined. WSPS significantly decreased ROS and MDA levels which is consistent with increased activity of superoxide dismutase (SOD). Meanwhile, WSPS upregulated the expression of stress resistance genes sod-1, sod-5, hsf-1, hsp-12.6, hsp-16.2, skn-1 and gst-4. Together, these results suggest that the anti-aging activity of WSPS under heat stress was mediated most likely by activation of the target genes of heat-shock transcription factor (HSF)-1 and skinhead (SKN)-1, and thus inducing endogenous ROS scavenging response.

Highly efficient removal and detoxification of phenolic compounds using persulfate activated by MnOx@OMC: Synergistic mechanism and kinetic analysis.

Persulfate-based advanced oxidation technology exhibits great potential for hazardous organic pollutant removal from wastewater. Acceleration of pollutant degradation needs to be elucidated, particularly for heterogeneous catalytic systems. In this study, manganese oxide ordered mesoporous carbon composites (MnOx@OMC) were prepared by nano-casting method and used for persulfate activation to degrade phenol. Kinetics analysis indicate that the rate of phenol degradation using MnOx@OMC composites was improved by 34.9 folds relative to that using a mixture of MnOx and OMC. The phenol toxicity towards Caenorhabditis elegans could be totally reduced within 8 min. The different roles of MnOx and OMC in persulfate activation were confirmed to validate their synergistic effect. MnOx provided major active sites for persulfate activation in accordance with the surface Mn3+/Mn4+ cycle to induce SO4•- radicals. The OMC matrix provided the adsorption sites to enrich phenol molecules on the catalytic surface and promote the interfacial electron transfer process for persulfate activation. Moreover, a novel kinetic model with two distinct kinetic stages was established to verify the effects of phenol and persulfate on phenol removal.

Toxic effects of prolonged exposure to [C14mim]Br on Caenorhabditis elegans.

Ionic liquids (ILs) are gradually concerned due to their potential environmental and health risks. In this work, the chronic effects of imidazolium-based ILs, using [C14mim]Br as a representative, were evaluated using model animal Caenorhabditis elegans. Our results show that prolonged exposure (72 h) of ILs to the nematodes at concentrations of 5 and 10 mg/L induced adverse effects on the growth, locomotive behaviors and development. To explore the toxicity mechanism, lipofuscin content, ROS level and the expressions of five superoxide dismutase (SOD) genes were determined after the prolonged exposure. The lipofuscin content, ROS level and expressions of SOD genes did not show significant changes except that the expression of sod-5 was reduced by 2.7-fold following the treatment of 10 mg/L of [C14mim]Br. These results suggest that oxidative stress may not be responsible for the adverse physiological effects induced by relatively low concentrations of imidazolium-based ILs. We further determined the gene expressions of phase I detoxification enzyme cytochrome P450 (CYP), phase II detoxification enzyme UDP-glucuronosyltransferase (UGT) and ATP-binding cassette (ABC) transporter P-glycoprotein (PGP). The results demonstrate that CYP, UGT and PGP may be involved in the detoxification of ILs. Our findings will aid in understanding the mechanisms of both toxicity and detoxification of imidazolium-based ILs in animals.