Pangenome and multi-tissue gene atlas provide new insights into the domestication and highland adaptation of yaks.

BACKGROUND: The genetic diversity of yak, a key domestic animal on the Qinghai-Tibetan Plateau (QTP), is a vital resource for domestication and breeding efforts. This study presents the first yak pangenome obtained through the de novo assembly of 16 yak genomes. RESULTS: We discovered 290 Mb of nonreference sequences and 504 new genes. Our pangenome-wide presence and absence variation (PAV) analysis revealed 5,120 PAV-related genes, highlighting a wide range of variety-specific genes and genes with varying frequencies across yak populations. Principal component analysis (PCA) based on binary gene PAV data classified yaks into three new groups: wild, domestic, and Jinchuan. Moreover, we proposed a 'two-haplotype genomic hybridization model' for understanding the hybridization patterns among breeds by integrating gene frequency, heterozygosity, and gene PAV data. A gene PAV-GWAS identified a novel gene (BosGru3G009179) that may be associated with the multirib trait in Jinchuan yaks. Furthermore, an integrated transcriptome and pangenome analysis highlighted the significant differences in the expression of core genes and the mutational burden of differentially expressed genes between yaks from high and low altitudes. Transcriptome analysis across multiple species revealed that yaks have the most unique differentially expressed mRNAs and lncRNAs (between high- and low-altitude regions), especially in the heart and lungs, when comparing high- and low-altitude adaptations. CONCLUSIONS: The yak pangenome offers a comprehensive resource and new insights for functional genomic studies, supporting future biological research and breeding strategies.

Silver sulfide anchored bismuth molybdate p-n heterojunction nano-coating with excellent photo-thermal self-healing performance.

In this research, a self-healing nano-coating with excellent photo-thermal response to near-infrared (NIR) laser is prepared. This coating incorporates silver sulfide anchored bismuth molybdate (Ag2S@Bi2MoO6) into a shape memory epoxy resin to achieve for a good photo-thermal conversion capability. The Ag2S@Bi2MoO6 p-n heterojunction could photo-generate more electron-holes pairs under the NIR laser irradiation. Also, it shows a wider absorption range of visible light, leading to effectively absorb the light energy, generate enough heat to induce the shape memory recovery in the coating, and seal the scratch. The results indicate that the temperature of EP-1 % Ag2S@Bi2MoO6 coating has reached about 88 °C, while good self-healing and anti-corrosion properties with a self-healing rate of 88.41 % have been achieved. Furthermore, calculations based on Density Functional Theory and Finite Element Method pointed out that the formation of p-n heterojunction effectively has enhanced the photo-thermal effect. This research opens a new way for developing self-healing coatings with an ultra-fast response time and high self-healing efficiency.

The involvement of the mitochondrial membrane in drug delivery.

Treatment effectiveness and biosafety are critical for disease therapy. Bio-membrane modification facilitates the homologous targeting of drugs in vivo by exploiting unique antibodies or antigens, thereby enhancing therapeutic efficacy while ensuring biosafety. To further enhance the precision of disease treatment, future research should shift focus from targeted cellular delivery to targeted subcellular delivery. As the cellular powerhouses, mitochondria play an indispensable role in cell growth and regulation and are closely involved in many diseases (e.g., cancer, cardiovascular, and neurodegenerative diseases). The double-layer membrane wrapped on the surface of mitochondria not only maintains the stability of their internal environment but also plays a crucial role in fundamental biological processes, such as energy generation, metabolite transport, and information communication. A growing body of evidence suggests that various diseases are tightly related to mitochondrial imbalance. Moreover, mitochondria-targeted strategies hold great potential to decrease therapeutic threshold dosage, minimize side effects, and promote the development of precision medicine. Herein, we introduce the structure and function of mitochondrial membranes, summarize and discuss the important role of mitochondrial membrane-targeting materials in disease diagnosis/treatment, and expound the advantages of mitochondrial membrane-assisted drug delivery for disease diagnosis, treatment, and biosafety. This review helps readers understand mitochondria-targeted therapies and promotes the application of mitochondrial membranes in drug delivery. STATEMENT OF SIGNIFICANCE: Bio-membrane modification facilitates the homologous targeting of drugs in vivo by exploiting unique antibodies or antigens, thereby enhancing therapeutic efficacy while ensuring biosafety. Compared to cell-targeted treatment, targeting of mitochondria for drug delivery offers higher efficiency and improved biosafety and will promote the development of precision medicine. As a natural material, the mitochondrial membrane exhibits excellent biocompatibility and can serve as a carrier for mitochondria-targeted delivery. This review provides an overview of the structure and function of mitochondrial membranes and explores the potential benefits of utilizing mitochondrial membrane-assisted drug delivery for disease treatment and biosafety. The aim of this review is to enhance readers' comprehension of mitochondrial targeted therapy and to advance the utilization of mitochondrial membrane in drug delivery.

Screening of Deoxynivalenol Cyclic Heptapeptide Mimotope Antigen.

In this study, phage clones that can bind to DON were selected from the phage cyclohepta peptide library by screening through the principle of solid-phase affinity, and mimotope were synthesized to replace the DON toxin standard to establish a green low toxicity detection system. The author conducted four rounds of screening in the phage cyclic heptapeptide library with DON-10a1a monoclonal antibody as the target molecule. Then 38 phage clones were selected and validated, and the results showed that 35 of them could bind to the DON-10a1a monoclonal antibody and were inhibited by DON toxin. Finally, the DNA was extracted and sequenced to obtain 6 different DNA sequences, which were named D1-D6 respectively. The peptides synthesized according to the corresponding amino acid sequences can replace DON toxin to establish a series of green and low toxicity assays.

From air to airway: Dynamics and risk of inhalable bacteria in municipal solid waste treatment systems.

Municipal solid waste treatment (MSWT) system emits a cocktail of microorganisms that jeopardize environmental and public health. However, the dynamics and risks of airborne microbiota associated with MSWT are poorly understood. Here, we analyzed the bacterial community of inhalable air particulates (PM10, n = 71) and the potentially exposed on-site workers' throat swabs (n = 30) along with waste treatment chain in Shanghai, the largest city of China. Overall, the airborne bacteria varied largely in composition and abundance during the treatment (P < 0.05), especially in winter. Compared to the air conditions, MSWT-sources that contributed to 15 ∼ 70% of airborne bacteria more heavily influenced the PM10-laden bacterial communities (PLS-SEM, ß = 0.40, P < 0.05). Moreover, our year-span analysis found PM10 as an important media spreading pathogens (104 ∼ 108 copies/day) into on-site workers. The machine-learning identified Lactobacillus and Streptococcus as pharynx-niched featured biomarker in summer and Rhodococcus and Capnocytophaga in winter (RandomForest, ntree = 500, mtry = 10, cross = 10, OOB = 0%), which closely related to their airborne counterparts (Procrustes test, P < 0.05), suggesting that MSWT a dynamic hotspot of airborne bacteria with the pronounced inhalable risks to the neighboring communities.

Catalytic Modification of Porous Two-Dimensional Ni-MOFs on Portable Electrochemical Paper-Based Sensors for Glucose and Hydrogen Peroxide Detection.

Rapid and accurate detection of changes in glucose (Glu) and hydrogen peroxide (H2O2) concentrations is essential for the predictive diagnosis of diseases. Electrochemical biosensors exhibiting high sensitivity, reliable selectivity, and rapid response provide an advantageous and promising solution. A porous two-dimensional conductive metal-organic framework (cMOF), Ni-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene), was prepared by using a one-pot method. Subsequently, it was employed to construct enzyme-free paper-based electrochemical sensors by applying mass-producing screen-printing and inkjet-printing techniques. These sensors effectively determined Glu and H2O2 concentrations, achieving low limits of detection of 1.30 µM and 2.13 µM, and high sensitivities of 5573.21 µA µM-1 cm-2 and 179.85 µA µM-1 cm-2, respectively. More importantly, the Ni-HHTP-based electrochemical sensors showed an ability to analyze real biological samples by successfully distinguishing human serum from artificial sweat samples. This work provides a new perspective for the use of cMOFs in the field of enzyme-free electrochemical sensing, highlighting their potential for future applications in the design and development of new multifunctional and high-performance flexible electronic sensors.

Effects of excessive weight gain during pregnancy on offspring health: a review / 预防医学

@#Excessive gestational weight gain has already become a global clinical and public health problem that seriously affects maternal health. Excessive gestational weight gain not only increases the cesarean section rate and induces adverse pregnant outcomes, but also affects offspring development and health. This article reviews the effects of excessive weight gain during pregnancy on offspring health and its underlying mechanisms. Excessive gestational weight gain may increase the risk of obesity, cardiovascular diseases, infectious diseases of the respiratory tract, diabetes, polycystic ovary syndrome, mental or psychological illness among offspring, and the pathophysiological mechanisms include inflammatory response, intestinal flora dysbiosis and epigenetics theory. However, further studies are required to validate these hypotheses and to evaluate the effect of excessive weight gain at different gestational stages on offspring health, so as to provide insights into reasonable management of weight gain during pregnancy and improvements of offspring health.

Optical flexible biosensors: From detection principles to biomedical applications.

Optical flexible biosensors are novel sensors fabricated on flexible or ductile materials that are used for the detection of analytes. Compared to traditional sensors, these biosensors offer greater flexibility, which allows them to adapt to different working environments, to meet the deformation requirements of humans. Flexible devices can not only detect alterations in analytes in vitro, but can also realize real-time and non-invasive monitoring of the variation of physical conditions or metabolites in vivo. Flexible devices are earning increasing attention from researchers and clinicians. In the present review, we summarize and introduce the detection principles, key analytes, and applications of optical flexible biosensors in the diagnosis/treatment of diseases as well as health detection. Moreover, the remaining challenges of flexible devices and their perspectives have also been addressed. We hope that this review will pave ways for the development of more feasible and multifunctional flexible devices.

Overview of the structure, side effects, and activity assays of l-asparaginase as a therapy drug of acute lymphoblastic leukemia.

l-Asparaginase (l-ASNase is the abbreviation, l-asparagine aminohydrolase, E.C.3.5.1.1) is an enzyme that is clinically employed as an antitumor agent for the treatment of acute lymphoblastic leukemia (ALL). Although l-ASNase is known to deplete l-asparagine (l-Asn), causing cytotoxicity in leukemia cells, the specific molecular signaling pathways are not well defined. Because of the deficiencies in the production and administration of current formulations, the l-ASNase agent in clinical use is still associated with serious side effects, so controlling its dose and activity monitoring during therapy is crucial for improving the treatment success rate. Accordingly, it is urgent to summarize and develop effective analytical methods to detect l-ASNase activity in treatment. However, current reports on these detection methods are fragmented and also have not been systematically summarized and classified, thereby not only delaying the investigations of specific molecular mechanisms, but also hindering the development of novel detection methods. Herein, in this review, we provided a detailed summary of the l-ASNase structures, antitumor mechanism and side effects, and current detection approaches, such as fluorescence assays, colorimetric assays, spectroscopic assays and some other assays. All of them possess unique advantages and disadvantages, so it has been difficult to establish clear criteria for clinical application. We hope that this review will be of some value in promoting the development of l-ASNase activity detection methods.

Soil Fungal Community Composition and Diversity of Culturable Endophytic Fungi from Plant Roots in the Reclaimed Area of the Eastern Coast of China.

As an important resource for screening microbial strains capable of conferring stress tolerance in plants, the fungal community associated with the plants grown in stressful environments has received great attention. In this study, high-throughput sequencing was employed to study the rhizosphere fungal community in the reclaimed area (i.e., sites F, H, and T) of the eastern coast of China. Moreover, endophytic fungi from the root of six plant species colonizing the investigated sites were isolated and identified. The differences in soil physicochemical parameters, fungal diversity, and community structure were detected among the sampling sites and between the seasons. Ectomycorrhizal (ECM) fungi (e.g., genera Tuber and Geopora) were dominant at site F, which was characterized by high soil total carbon (SC) and total nitrogen (SN) contents and low soil electrical conductivity (EC) value. Arbuscular mycorrhizal (AM) fungi, including genera Glomus, Rhizophagus, and Entrophospora were dominant at sites H (winter), H (summer), and T (summer), respectively. The positive relationship between the EC value and the abundance of genus Glomus indicated the ability of this AM fungus to protect plants against the salt stress. Endophytic fungi at sites F (Aspergillus and Tetracladium), H (Nigrospora), and T (Nigrospora, Coniochaeta and Zopfiella) were recognized as the biomarkers or keystone taxa, among which only genus Aspergillus was isolated from the plant roots. The aforementioned AM fungi and endophytic fungi could contribute to the promotion of plant growth in the newly reclaimed land.

Optical/electrochemical methods for detecting mitochondrial energy metabolism.

This review highlights the biological importance of mitochondrial energy metabolism and the applications of multiple optical/electrochemical approaches to determine energy metabolites. Mitochondria, the main sites of oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis, provide the majority of energy required by aerobic cells for maintaining their physiological activity. They also participate in cell growth, differentiation, information transmission, and apoptosis. Multiple mitochondrial diseases, caused by internal or external factors, including oxidative stress, intense fluctuations of the ionic concentration, abnormal oxidative phosphorylation, changes in electron transport chain complex enzymes and mutations in mitochondrial DNA, can occur during mitochondrial energy metabolism. Therefore, developing accurate, sensitive, and specific methods for the in vivo and in vitro detection of mitochondrial energy metabolites is of great importance. In this review, we summarise the mitochondrial structure, functions, and crucial energy metabolic signalling pathways. The mechanism and applications of different optical/electrochemical methods are thoroughly reviewed. Finally, future research directions and challenges are proposed.

[Anatomic and clinical study of virtual reality technology assisted modified transtrochanteric curved varus osteotomy for osteonecrosis of the femoral head].

OBJECTIVE: To explore the feasibility and effectiveness of the modified transtrochanteric curved varus osteotomy in the treatment of osteonecrosis of the femoral head (ONFH), clarify the key points of the operation, and then explore the effectiveness of modified transtrochanteric curved varus osteotomy in the treatment of ONFH assisted by virtual reality (VR) technology. METHODS: A 70-year-old adult female cadaver without formaldehyde fixation was taken. It was confirmed by anatomical study and simulated operation that the modified transtrochanteric curved varus osteotomy was suitable for type C1 (patients with involvement of the lateral column of the femoral head but partial integrity) classified by the Japanese Osteonecrosis Investigation Committee (JIC). Between October 2018 and August 2020, 11 patients (17 hips) with ONFH who met the selection criteria were treated with modified transtrochanteric curved varus osteotomy. VR technology was used to simulate varus osteotomy before operation to predict the angle of valgus of lower limbs and pronation of femoral head. Osteotomy, valgus, and pronation were performed according to the results of preoperative planning. After operation, X-ray films were used to evaluate the changes of varus and neck-shaft angle after VR assisted surgery, and Harris score was used to evaluate the hip function. RESULTS: The anteroposterior pelvic X-ray film was rechecked at 2 days after operation, of which 3 hips were consistent with the planned varus angle of VR preoperative planning, and the error value of varus angle of the remaining 14 hips was 1°-4°. The difference between VR preoperative planning and 2 days after operation was 6°-16°. All 11 patients were followed up 11-28 months, with an average of 19.2 months. All incisions healed by first intension. During the follow-up, 1 case (1 hip) developed greater trochanter fracture at 2 months after operation and was treated with open reduction and plate and screw internal fixation; 1 case (1 hip) had delayed healing at osteotomy at 4 months after operation and healed at 3 months after local injection of platelet rich plasma and oral supplementation of kidney blood-strengthening soup. At last follow-up, 17 hip osteotomies healed. The Harris score was 84.0±5.6, which was significantly higher than that before operation (57.2±5.5) ( t=-14.107, P=0.000); hip function was excellent in 2 hips, good in 13 hips, and fair in 2 hips. CONCLUSION: The modified transtrochanteric curved varus osteotomy for the treatment of ONFH is theoretically feasible, and the short-term effectiveness of this operation combined with VR technology is satisfactory.

Wearable Sweat Biosensors Refresh Personalized Health/Medical Diagnostics.

Sweat contains a broad range of critical biomarkers including ions, small molecules, and macromolecules that may indirectly or directly reflect the health status of the human body and thereby help track disease progression. Wearable sweat biosensors enable the collection and analysis of sweat in situ, achieving real-time, continuous, and noninvasive monitoring of human biochemical parameters at the molecular level. This review summarizes the physiological/pathological information of sweat and wearable sweat biosensors. First, the production of sweat pertaining to various electrolytes, metabolites, and proteins is described. Then, the compositions of the wearable sweat biosensors are summarized, and the design of each subsystem is introduced in detail. The latest applications of wearable sweat biosensors for outdoor, hospital, and family monitoring are highlighted. Finally, the review provides a summary and an outlook on the future developments and challenges of wearable sweat biosensors with the aim of advancing the field of wearable sweat monitoring technology.

Near infrared photothermal conversion materials: mechanism, preparation, and photothermal cancer therapy applications.

Photothermal therapy (PTT) has been widely applied in cancer therapy as a result of its non-invasive, localized treatment and good therapeutic effect. In general, the final therapeutic effect of PTT mainly depends on the photothermal materials, which can be further considered to be determined by the photothermal conversion efficiency, biocompatibility, and photothermal stability of photothermal materials. In this review, photothermal materials including inorganic materials, organic materials, and organic-inorganic composite materials in recent years have been summarized in terms of the mechanism, preparation, and cancer therapy applications. In the end, the perspectives and obstacles in their further development are overviewed.

Mito-Bomb: Targeting Mitochondria for Cancer Therapy.

Cancer has been one of the most common life-threatening diseases for a long time. Traditional cancer therapies such as surgery, chemotherapy (CT), and radiotherapy (RT) have limited effects due to drug resistance, unsatisfactory treatment efficiency, and side effects. In recent years, photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT) have been utilized for cancer treatment owing to their high selectivity, minor resistance, and minimal toxicity. Accumulating evidence has demonstrated that selective delivery of drugs to specific subcellular organelles can significantly enhance the efficiency of cancer therapy. Mitochondria-targeting therapeutic strategies are promising for cancer therapy, which is attributed to the essential role of mitochondria in the regulation of cancer cell apoptosis, metabolism, and more vulnerable to hyperthermia and oxidative damage. Herein, the rational design, functionalization, and applications of diverse mitochondria-targeting units, involving organic phosphine/sulfur salts, quaternary ammonium (QA) salts, peptides, transition-metal complexes, guanidinium or bisguanidinium, as well as mitochondria-targeting cancer therapies including PDT, PTT, CDT, and others are summarized. This review aims to furnish researchers with deep insights and hints in the design and applications of novel mitochondria-targeting agents for cancer therapy.

Simultaneously Detecting Monoamine Oxidase A and B in Disease Cell/Tissue Samples Using Paper-Based Devices.

As enzymes in the outer membrane of the mitochondrion, monoamine oxidases (MAOs) can catalyze the oxidative deamination of monoamines in the human body. According to different substrates, MAOs can be divided into MAO-A and MAO-B. The imbalance of the MAO-A is associated with neurological degeneration, while excess MAO-B activity is closely connected with Parkinson's disease (PD) and Alzheimer's disease (AD); therefore, detection of MAOs is of great significance for the diagnosis and treatment of these diseases. This work reports the multiplexed detection of MAO-A and MAO-B using paper-based devices based on chemiluminescence (CL). The detection limits were 5.01 pg/mL for MAO-A and 8.50 pg/mL for MAO-B in human serum. In addition, we used paper-based devices to detect MAOs in human cells and tissue samples and found that the results of paper-based detection and Western blotting (WB) showed the same trend. While only one antibody can be incubated on the same membrane by WB, multiple antibodies incubated on the same paper enabled simultaneous detection of MAO-A and MAO-B by paper-based devices. The paper-based assay could be used for preliminary early screening of clinical samples for MAOs and can be extended as an alternative to WB for multiplexed detection of various proteins in disease cell or tissue samples.

Population genome of the newly discovered Jinchuan yak to understand its adaptive evolution in extreme environments and generation mechanism of the multirib trait.

The adaptation and diversity of animals to the extreme environments of the Qinghai-Tibet Plateau (QTP) are typical materials to study adaptive evolution. The recently discovered Jinchuan yak population has many individuals with multiple ribs. However, little is known about this yak's origin, evolution, and the genetic mechanisms that formed its unique multirib trait. Here, we report a valuable population genome resource of the Jinchuan yak by resequencing the whole genome of 150 individuals. Population genetic polymorphism and structure analysis reveal that Jinchuan yak can be differentiated as a unique and original yak population among the domestic yak. Combined with geological change, the Jinchuan yak's evolutionary origin is speculated to be about 6290 years ago, which may be related to the unique geographical environment of the eastern edge of the QTP during this period. Compared with other domestic yaks, this new population has 280 positively selected genes. The genes related to skeletal function hold a considerable and remarkable proportion, suggesting that the specific skeletal characteristics have been enhanced in the adaptive evolution of Jinchuan yak in the extreme plateau environment. The genome-wide association study has revealed that TUBA8 and TUBA4A, the genes that regulate the cytoskeleton, are potential genes associated with the multirib trait. Our findings provide a basis to further understand the generation mechanism of the adaptive evolution of this new population in high-altitude extreme environments and the multivertebrate trait of domestic animals.

Embedding Silver Nanowires into a Hydroxypropyl Methyl Cellulose Film for Flexible Electrochromic Devices with High Electromechanical Stability.

Transparent conductive films (TCFs) based on silver nanowires (AgNWs) are becoming one of the best candidates in realizing flexible optoelectronic devices. The AgNW-based TCF is usually prepared by coating AgNWs on a transparent polymer film; however, the coated AgNWs easily detach from the polymer underneath because of the weak adhesion between them. Herein, a network of AgNWs is embedded in the transparent hydroxypropyl methyl cellulose film, which has a strong adhesion with the AgNWs. The obtained TCF shows high optical transmittance (>85%), low roughness (rms = 4.8 ± 0.5 nm), and low haze (<0.2%). More importantly, owing to the embedding structure and strong adhesion, this TCF also shows excellent electromechanical stability, which is superior to the reported ones. Employing this TCF in a flexible electrochromic device, the obtained device exhibits excellent cyclic electromechanical stability and high coloring efficiency. Our work demonstrates a promising TCF with superior electromechanical stability for future applications in flexible optoelectronics.

Photosensitive hydrogels: from structure, mechanisms, design to bioapplications.

Hydrogel is a smart material with a three-dimensional network structure and has been widely used in various fields due to its good biodegradability, biocompatibility, and modification. Photosensitive hydrogel is a smart hydrogel, and its amenability to remote, precise control, and flexible and convenient regulation of stimulating factors make it an ideal candidate for use in fields such as biological materials, drug carriers, and sensors. In this review, we discuss the structure, mechanisms, design principles, and bioapplications of photosensitive hydrogels as developed in recent years. Finally, their potential for development and potential future challenges are outlined.