The Golgi Outpost Protein TPPP Nucleates Microtubules and Is Critical for Myelination.

Oligodendrocytes extend elaborate microtubule arbors that contact up to 50 axon segments per cell, then spiral around myelin sheaths, penetrating from outer to inner layers. However, how they establish this complex cytoarchitecture is unclear. Here, we show that oligodendrocytes contain Golgi outposts, an organelle that can function as an acentrosomal microtubule-organizing center (MTOC). We identify a specific marker for Golgi outposts-TPPP (tubulin polymerization promoting protein)-that we use to purify this organelle and characterize its proteome. In in vitro cell-free assays, recombinant TPPP nucleates microtubules. Primary oligodendrocytes from Tppp knockout (KO) mice have aberrant microtubule branching, mixed microtubule polarity, and shorter myelin sheaths when cultured on 3-dimensional (3D) microfibers. Tppp KO mice exhibit hypomyelination with shorter, thinner myelin sheaths and motor coordination deficits. Together, our data demonstrate that microtubule nucleation outside the cell body at Golgi outposts by TPPP is critical for elongation of the myelin sheath.

Dysregulation of myelination-related genes in schizophrenia.

Schizophrenic individuals display disrupted myelination patterns, altered oligodendrocyte distribution, and abnormal oligodendrocyte morphology. Schizophrenia is linked with dysregulation of a variety of genes involved in oligodendrocyte function and myelin production. Single-nucleotide polymorphisms (SNPs) and rare mutations in myelination-related genes are observed in certain schizophrenic populations, representing potential genetic risk factors. Downregulation of myelination-related RNAs and proteins, particularly in frontal and limbic regions, is consistently associated with the disorder across multiple studies. These findings support the notion that disruptions in myelination may contribute to the cognitive and behavioral impairments experienced in schizophrenia, although further evidence of causation is needed.

Activation of the cGMP/PKG/ERK signaling pathway associated with PDE5Is inhibits fibroblast activation by downregulating autophagy in early progressive benign prostatic hyperplasia.

PURPOSE: Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases affecting aging males. However, approximately, 8% of the BPH patients under 50-year-old experience remarkably early progression, for reasons that remain elusive. Among the various factors implicated in promoting BPH advancement, the activation of fibroblasts and autophagy hold particular importance. Our research endeavors to explore the mechanisms behind the accelerated progression in these patients. METHODS: Immunohistochemistry and immunofluorescence were performed to detect the expression levels of LC3, p62, PDE5, and α-SMA in diverse BPH tissues and prostate stromal cells. The autophagy activator rapamycin, the autophagy suppressor chloroquine, and siRNA transfection were used to identify the impact of autophagy on fibroblast activation. RESULTS: Prostatic stromal fibroblasts in early progressive BPH tissues displayed activation of autophagy with an upregulation of LC3 and a concurrent downregulation of p62. After starvation or rapamycin treatment to a heightened level of autophagy, fibroblasts exhibited activation. Conversely, chloroquine treatment and ATG-7-knockdown effectively suppressed the level of autophagy and fibroblast activation. High expression of PDE5 was found in early progressive BPH stromal cells. The administration of PDE5 inhibitors (PDE5Is) hindered fibroblast activation through suppressing autophagy by inhibiting the ERK signaling pathway. CONCLUSION: Our findings suggest that autophagy plays a pivotal role in promoting BPH progression through fibroblast activation, while PDE5Is effectively suppress autophagy and fibroblast activation via the ERK signaling pathway. Nevertheless, further investigations are warranted to comprehensively elucidate the role of autophagy in BPH progression.

Association of critical hypoperfusion biomarkers on CT with futile recanalization and poor outcome after mechanical thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: We aimed to investigate the association between critical perfusion delay and poor outcome among recanalized stroke patients with anterior large-vessel occlusion, and to use pretreatment hypoperfusion biomarkers on CT to predict futile recanalization even after successful thrombectomy. METHODS: An ischemic region with time-to-maximum (Tmax) > 12s-10s was defined as critical hypoperfusion, Tmax > 8s as moderate hypoperfusion, and hypoperfusion intensity ratio (HIR, volumetric ratio of Tmax > 10s / Tmax > 6s) represented for severity of critical hypoperfusion and rCBF < 30% for ischemic core. The associations between these CT perfusion characteristics and favorable or unfavorable outcome (mRS 0-2 versus 3-6) were analyzed in univariable regression, and a multivariable model was then used to predict futile recanalization. RESULTS: Seventy-nine stroke patients were included and had good grades of instant recanalization. Forty-two patients (53%) had poor outcomes, and they had a significantly larger volume of critical hypoperfusion as seen with Tmax > 10s and > 12s (P = 0.032 and 0.008, respectively), a larger volume of ischemic core (P = 0.011) and a higher HIR (P = 0.002) than those patients achieving good outcomes. In the univariable analysis, a lower HIR (OR, 0.008; 95%CI, 0.001-0.254, P = 0.006) was associated with favorable outcome. The volume size of Tmax > 12s was significantly and positively correlated with the size of ischemic core. A HIR value higher than 0.491 might predict a futile recanalization and poor outcome (AUC = 0.701). CONCLUSIONS: The critical hypoperfusion biomarkers on CTP could be useful in triaging endovascular treatment and identifying stroke patients at risk of futile recanalization.

Analysis of risk factors for carotid artery plaque in asymptomatic adults.

OBJECTIVE: This study aimed to investigate the risk factors affecting the presence of carotid plaque in asymptomatic adults. METHODS: Asymptomatic adults (age > 40 years, no symptoms of cardiovascular and cerebrovascular diseases) undergoing routine health examinations from physical examination department were included in this study. Carotid plaque was measured by Resona 7OB and Resona 8EXP color Doppler ultrasound and L9-3U and L4-5WU probes. The focal carotid intima-media thickness was greater than 1.1 mm, and the local protrusion of the artery wall into the artery lumen suggested the presence of carotid atherosclerotic plaque. According to their ultrasound results, 1077 asymptomatic adults were divided into a group with carotid plaque (477) and a group without carotid plaque (600). RESULTS: A total of 1077 asymptomatic adults were included in this study, of whom 44.3% had carotid plaque. The proportion of men with carotid plaque was 84.5%. Multifactorial logistic analysis suggested that age, fasting blood glucose (FBG), total cholesterol (TC), homocysteine (Hcy) and male gender were risk factors for carotid atherosclerosis. The predictive probability of these risk factor indicators derived from the multifactorial model was calculated using receiver operating characteristic (ROC) curves with SPSS 25.0 software. The calculated area under the receiver operating characteristic curve (AUC) was 0.715 (95% CI, 0.685-0.746). CONCLUSION: Age, FBG, TC, Hcy and male gender are risk factors for carotid atherosclerosis in asymptomatic adults. Gender differences in carotid atherosclerosis deserve further attention.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Chinese expert consensus on management of antifungal-resistant dermatophytoses (2024 edition).

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.

Building Sustainable Saturated Fatty Acid-Zinc Interfacial Layer toward Ultra-Stable Zinc Metal Anodes.

The commercialization pace of aqueous zinc batteries (AZBs) is seriously limited due to the uncontrolled dendrite growth and severe corrosion reaction of the zinc anode. Herein, a universal and extendable saturated fatty acid-zinc interfacial layer strategy for modulating the interfacial redox process of zinc toward ultrastable Zn metal anodes is proposed. The in situ complexing of saturated fatty acid-zinc interphases could construct an extremely thin zinc compound layer with continuously constructed zincophilic sites which kinetically regulates Zn nucleation and deposition behaviors. Furthermore, the multifunctional interfacial layer with internal hydrophobic carbon chains as a protective layer is efficient to exclude active water molecules from the surface and efficiently inhibit the surface corrosion of zinc. Consequently, the modified anode shows a long cycle life of over 4000 h at 5 mA cm-2. In addition, the assembled Zn||V2O5 full cells based on modified zinc anodes have excellent rate performance and long cycle stability.

Promoting Piezocatalytic H2 O2 Production in Pure Water by Loading Metal-Organic Cage-Modified Gold Nanoparticles on Graphitic Carbon Nitride.

Piezocatalytic hydrogen peroxide (H2 O2 ) production is a green synthesis method, but the rapid complexation of charge carriers in piezocatalysts and the difficulty of adsorbing substrates limit its performance. Here, metal-organic cage-coated gold nanoparticles are anchored on graphitic carbon nitride (MOC-AuNP/g-C3 N4 ) via hydrogen bond to serve as the multifunctional sites for efficient H2 O2 production. Experiments and theoretical calculations prove that MOC-AuNP/g-C3 N4 simultaneously optimize three key parts of piezocatalytic H2 O2 production: i) the MOC component enhances substrate (O2 ) and product (H2 O2 ) adsorption via host-guest interaction and hinders the rapid decomposition of H2 O2 on MOC-AuNP/g-C3 N4 , ii) the AuNP component affords a strong interfacial electric field that significantly promotes the migration of electrons from g-C3 N4 for O2 reduction reaction (ORR), iii) holes are used for H2 O oxidation reaction (WOR) to produce O2 and H+ to further promote ORR. Thus, MOC-AuNP/g-C3 N4 can be used as an efficient piezocatalyst to generate H2 O2 at rates up to 120.21 µmol g-1 h-1 in air and pure water without using sacrificial agents. This work proposes a new strategy for efficient piezocatalytic H2 O2 synthesis by constructing multiple active sites in semiconductor catalysts via hydrogen bonding, by enhancing substrate adsorption, rapid separation of electron-hole pairs and preventing rapid decomposition of H2 O2 .

Cross-disease characterization of fibroblast heterogeneities and their pathogenic roles in skin inflammation.

Fibroblasts are critical pro-inflammatory regulators in chronic inflammatory and fibrotic skin diseases. However, fibroblast heterogeneity and the absence of a unified cross-disease taxonomy have hindered our understanding of the shared/distinct pathways in non-communicable skin inflammation. By integrating 10× single-cell data from 75 skin samples, we constructed a single-cell atlas across inflammatory and fibrotic skin diseases and identified 9 distinct subsets of skin fibroblasts. We found a shared subset of CCL19+ fibroblasts across these diseases, potentially attracting and educating immune cells. Moreover, COL6A5+ fibroblasts were a distinct subset implicated in the initiation and relapse of psoriasis, which tended to differentiate into CXCL1+ fibroblasts, inducing neutrophil chemotaxis and infiltration; while CXCL1+ fibroblasts exhibited a more heterogeneous response to certain inflammatory conditions. Differentiation trajectory and regulatory factors of these fibroblast subsets were also revealed. Therefore, our study presents a comprehensive atlas of skin fibroblasts and highlights pathogenic fibroblast subsets in skin disorders.

Effect of SHR0302 on the pharmacokinetics of CYP3A4, CYP2C8, CYP2C9 and CYP2C19 probe substrates in healthy volunteers: A cocktail analysis.

AIMS: This study evaluated the effects of SHR0302 on the pharmacokinetics of cytochrome P450 (CYP) probe substrates. METHODS: We performed a single-centre, open-label, three-period drug-drug interaction (DDI) study in 24 healthy subjects (NCT05392127). Subjects received a single oral dose of 5 mg warfarin (CYP2C9), 20 mg omeprazole (CYP2C19) and 15 mg midazolam (CYP3A4) on Days 1, 8 and 22, and received 0.5 mg repaglinide (CYP2C8) on Days 7, 14 and 28. Multiple oral doses of 8 mg SHR0302 were administered once daily from Day 8 to Day 28. RESULTS: The exposure of S-warfarin and repaglinide were comparable before and after SHR0302 administration. AUC of midazolam was not affected by SHR0302, whereas the administration of SHR0302 slightly decreased the Cmax of midazolam by 7.6% (single dose) and 15.7% (once daily for 14 days). The AUC0-t , AUC0-inf , and Cmax of omeprazole were slightly decreased after a single dose of SHR0302 by 19.2%, 21.8% and 23.5%, respectively. In the presence of SHR0302 for 14 days, the AUC0-t , AUC0-inf , and Cmax of omeprazole were marginally reduced by 3.0%, 16.4% and 8.3%, respectively. According to the induction mechanism of the CYP enzyme, for the investigation of the induction effect, the results of multiple administrations of the perpetrator were more reliable than those of the single dose. CONCLUSIONS: The results demonstrated that co-administration of SHR0302 8 mg once daily is unlikely to have a clinically meaningful effect on the exposure of drugs metabolized by CYP3A4, CYP2C8, CYP2C9 and CYP2C19 in healthy subjects.

Effect of CYP3A4 induction and inhibition on the pharmacokinetics of SHR0302 in healthy subjects.

AIMS: SHR0302 is a selective Janus kinase (JAK) 1 inhibitor under clinical investigation for the treatment of rheumatoid arthritis (RA). As SHR0302 is metabolized mainly by cytochrome P450 (CYP) 3A4, clinical studies were performed to evaluate the effects of a strong CYP3A4 inducer, rifampin, and a strong CYP3A4 inhibitor, itraconazole, on the pharmacokinetics of SHR0302 in healthy subjects. METHODS: Two phase I, open-label, fixed-sequence drug interaction studies enrolled 28 subjects. In Study A, 14 subjects received 8 mg SHR0302 on Days 1 and 10, and 600 mg rifampin once daily on Days 3-11. In Study B, 14 subjects received 4 mg SHR0302 on Days 1 and 8, and 200 mg itraconazole once daily on Days 4-10. Blood samples were collected to measure SHR0302 concentrations. Pharmacokinetic parameters were calculated using non-compartmental analysis. Treatment comparisons were made using mixed-effect models. RESULTS: Co-administration with rifampin decreased the exposures of SHR0302 with geometric mean ratios (GMRs) (90% confidence intervals [CIs]) for AUC0-inf of 0.51 (0.49, 0.54) and Cmax of 0.91 (0.84, 0.98). Co-administration with itraconazole increased the exposures of SHR0302 with GMR (90% CIs) for AUC0-inf of 1.48 (1.41, 1.56) and Cmax of 1.06 (0.982, 1.14). Single oral doses of SHR0302 administered with or without rifampin or itraconazole were generally safe. CONCLUSIONS: Strong CYP3A4 induction and inhibition both resulted in a weak effect on the clinical exposures of SHR0302. These present studies provided valuable information that helps inform SHR0302 dosing instructions and concomitant medication precautions.

Anti-ovarian cancer potential, in silico studies, and anti-Alzheimer's disease effects of some natural compounds as cholinesterase inhibitors.

Ovarian cancer ranks seventh in the most common malignant tumors in females and seriously threatens women's reproductive health. Natural sources may lead to basic research on potential bioactive components as lead compounds in drug discovery and, ultimately, therapeutic treatments for ovarian cancer and other diseases. Alzheimer's disease (AD) and ovarian cancer are complex diseases of aging that impose an enormous public health burden worldwide. Additionally, people with AD have low levels of acetylcholine in their brains. Enzymes called cholinesterases break down acetylcholine in the brain. If their action is inhibited, more acetylcholine is available for communication among brain cells. In this study, pregnanolone, diethylstilbestrol (DES), flavokawain C, and methyl 3,4,5-trihydroxybenzoate molecules obtained excellent-to-good inhibitory against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with IC50 values ranging between 77.18 ± 8.62 to 461.35 ± 28.54 µM for AChE and 23.86 ± 4.07 to 306.62 ± 32.46 µM for BuChE. The calculations revealed the probable interactions and their characteristics at an atomic level. Indeed, the docking scores of DES, flavokawain C, pregnanolone, and methyl 3,4,5-trihydroxybenzoate for AChE are -6.685, -6.247, -6.672, and -5.183 (kcal/mol), respectively. This value for the compounds against BuChE is -6.042, -8.851, -5.655, and -5.898 (kcal/mol), respectively. Additionally, these compounds significantly decreased ovarian cancer cell viability. Additionally, 100 µM dose of all molecules caused good reductions in ovarian cancer cell viability.

Ukraine refugee crisis: evolving needs and challenges.

This case report examines the initial experience of Poland in responding to the refugee crisis triggered by the war in Ukraine. In the first 2 months of the crisis, more than 3 million Ukrainian refugees fled to Poland. The large influx of refugees rapidly overwhelmed local services and led to a complex humanitarian emergency. The initial priorities were to address basic human needs, such as shelter, infectious disease concerns and healthcare access, but evolved to include mental health, non-communicable diseases and protection needs. This necessitated a 'whole of society' response involving multiple agencies and civil society. Emerging lessons learned include the need for ongoing needs assessments, robust disease monitoring and surveillance, as well as flexible multisectoral responses that are culturally sensitive. Finally, Poland's efforts to integrate refugees may help mitigate some of the adverse consequences of the conflict-related migration.

Characterizing the Spatio-Temporal Variations of Urban Growth with Multifractal Spectra.

Urban morphology exhibits fractal characteristics, which can be described by multifractal scaling. Multifractal parameters under positive moment orders primarily capture information about central areas characterized by relatively stable growth, while those under negative moment orders mainly reflect information about marginal areas that experience more active growth. However, effectively utilizing multifractal spectra to uncover the spatio-temporal variations of urban growth remains a challenge. To addresses this issue, this paper proposes a multifractal measurement by combining theoretical principles and empirical analysis. To capture the difference between growth stability in central areas and growth activity in marginal areas, an index based on generalized correlation dimension Dq is defined. This index takes the growth rate of Dq at extreme negative moment order as the numerator and that at extreme positive moment order as the denominator. During the stable stage of urban growth, the index demonstrates a consistent pattern over time, while during the active stage, the index may exhibit abnormal fluctuations or even jumps. This indicates that the index can reveal spatio-temporal information about urban evolution that cannot be directly observed through multifractal spectra alone. By integrating this index with multifractal spectra, we can more comprehensively characterize the evolutionary characteristics of urban spatial structure.

Enhanced phenotype of calcipotriol-induced atopic dermatitis in filaggrin-deficient mice.

Impaired function of filaggrin (FLG) is a major predisposing factor for atopic dermatitis (AD). Several studies on FLG-deficient (Flg-/- ) mice have indicated an essential role for FLG in the skin barrier and the development of AD, but none of the studies have described the characteristics on Flg-/- mice with calcipotriol (CPT)-induced atopic dermatitis, which restricts the comprehensive understanding of functions of FLG. The present study sought to generate Flg-/- mice and applied CPT to produce AD-like dermatitis for in vivo analysis of the FLG functions. CPT was applied on the skin of Flg-/- mice to establish the AD-like dermatitis mouse model. The lesion inflammation was evaluated by gross ear thickness, histopathology, immunofluorescence, and cytokine production. Also, mucopolysaccharide polysulfate (MPS) and ceramide were used to observe the therapeutic function in this model. The results showed that the inflammation of CPT-induced dermatitis in Flg-/- mice was more severer than that of wild-type (WT) mice, as evident by the increased level of gross appearance, ear thickness, inflammatory cell infiltration (mast cells and CD3+ T cells), and inflammatory cytokine expression (interleukin (IL)-4, IL-6, IL-13, and thymic stromal lymphopoietin (TSLP)). The emollients MPS and ceramide partially restored the epidermal function and alleviated the skin inflammation in Flg-/- mice with CPT-induced AD-like dermatitis. The current study demonstrated that skin barrier protein FLG is critical in the pathogenesis of AD. Also, the AD mouse model induced by CPT in Flg-/- mice could be utilized to search for drug targets in AD.

A Convenient Procedure for Preparing BiOX-TiO2 Photoelectrocatalytic Electrodes from a Titanium-Oxo Compound-Modified Carbon Fiber Cloth.

Photoelectrocatalysis (PEC) has shown great advantages in sustainable organic synthesis and wastewater treatment because the PEC process can minimize electron-hole recombination, thereby improving the photocatalytic performance. Here, we report a convenient procedure for preparing immobilized BiOX-TiO2 photoelectrocatalytic electrodes from a titanium-oxo compound (TOC)-modified carbon fiber cloth (CFC). Crystalline TOCs composed of Ti12 cations and bismuth halide anions, [Ti12O14(OiPr)18][Bi3Br11(THF)2] (1) and [Ti12O14(OiPr)18][Bi4I14(THF)2] (2), were grown on CFC. Taking advantage of the easy hydrolysis of the titanium-oxo cation and bismuth halide anion, we could easily transform these CFC-immobilized crystals into BiOX-TiO2/CFC (X = Br or I) photocatalysts, which facilitates recycling of the catalysts. The photocatalytic dye degradation test showed that the efficiency did not decrease obviously after 10 photocatalytic cycles. Using BiOX-TiO2-modified CFC as electrodes, electrocatalysis (EC), photocatalysis (PC), and PEC were examined. PEC showed an attractive synergistic effect of EC and PC. These TOC-modified CFCs would be potential candidates for catalytic electrodes for sustainable wastewater purification.

Development and validation of a deep learning algorithm based on fundus photographs for estimating the CAIDE dementia risk score.

BACKGROUND: the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score is a recognised tool for dementia risk stratification. However, its application is limited due to the requirements for multidimensional information and fasting blood draw. Consequently, an effective and non-invasive tool for screening individuals with high dementia risk in large population-based settings is urgently needed. METHODS: a deep learning algorithm based on fundus photographs for estimating the CAIDE dementia risk score was developed and internally validated by a medical check-up dataset included 271,864 participants in 19 province-level administrative regions of China, and externally validated based on an independent dataset included 20,690 check-up participants in Beijing. The performance for identifying individuals with high dementia risk (CAIDE dementia risk score ≥ 10 points) was evaluated by area under the receiver operating curve (AUC) with 95% confidence interval (CI). RESULTS: the algorithm achieved an AUC of 0.944 (95% CI: 0.939-0.950) in the internal validation group and 0.926 (95% CI: 0.913-0.939) in the external group, respectively. Besides, the estimated CAIDE dementia risk score derived from the algorithm was significantly associated with both comprehensive cognitive function and specific cognitive domains. CONCLUSIONS: this algorithm trained via fundus photographs could well identify individuals with high dementia risk in a population setting. Therefore, it has the potential to be utilised as a non-invasive and more expedient method for dementia risk stratification. It might also be adopted in dementia clinical trials, incorporated as inclusion criteria to efficiently select eligible participants.

The performance of detecting Mycobacterium tuberculosis complex in lung biopsy tissue by metagenomic next-generation sequencing.

BACKGROUND: Tuberculosis (TB) is a chronic infectious disease caused by the Mycobacterium tuberculosis complex (MTBC), which is the leading cause of death from infectious diseases. The rapid and accurate microbiological detection of the MTBC is crucial for the diagnosis and treatment of TB. Metagenomic next-generation sequencing (mNGS) has been shown to be a promising and satisfying application of detection in infectious diseases. However, relevant research about the difference in MTBC detection by mNGS between bronchoalveolar lavage fluid (BALF) and lung biopsy tissue specimens remains scarce. METHODS: We used mNGS to detect pathogens in BALF and lung biopsy tissue obtained by CT-guide percutaneous lung puncture (CPLP) or radial endobronchial ultrasound transbronchial lung biopsy (R-EBUS-TBLB) from 443 hospitalized patients in mainland China suspected of pulmonary infections between May 1, 2019 and October 31, 2021. Aim to evaluate the diagnostic performance of mNGS for detecting MTBC and explore differences in the microbial composition in the 2 specimen types. RESULTS: Among the 443 patients, 46 patients finally were diagnosed with TB, of which 36 patients were detected as MTBC positive by mNGS (8.93%). Striking differences were noticed in the higher detection efficiency of lung biopsy tissue compared with BALF (P = 0.004). There were no significant differences between the 2 specimen types in the relative abundance among the 27 pathogens detected by mNGS from the 36 patients. CONCLUSIONS: This study demonstrates that mNGS could offer an effective detection method of MTBC in BALF or lung tissue biopsy samples in patients suspected of TB infections. When it comes to the situations that BALF samples have limited value to catch pathogens for special lesion sites or the patients have contraindications to bronchoalveolar lavage (BAL) procedures, lung biopsy tissue is an optional specimen for MTBC detection by mNGS. However, whether lung tissue-mNGS is superior to BALF-mNGS in patients with MTBC infection requires further prospective multicenter randomized controlled studies with more cases.

The origin and domestication history of domestic horses and the domestication characteristics of breeds.

The horse (Equus caballus) was domesticated thousands of years after dog, cattle, pig, sheep, and goat. Importantly, it represents the domestic animal that mostly impacted the development of human civilization. Its excellent loading and moving ability prompted the changes from fixed farming mode into mobile sharing mode. Accordingly, its domestication history deserves considerable attention. So far, many issues have long been controversial, due to the extinction of the closest wild relatives and the dramatic reduction of genetic diversity. With the continuous development of sequencing technology and the utilization of ancient samples, we got more clues to the origin and domestication process. In this review, we summarize 1) current progresses on the domestication history revealed by nuclear genes, mtDNA, Y chromosome, and ancient DNA, 2) the characteristics of population structure and diversification among modern breeds, 3) the genetic basis of important phenotypes, such as coat color, speed, and body size. The overall aim of the review is to provide in-depth insights into the studies of horse domestication, the preservation and utilization of genetic resources, the direction of breeding improvement, and the development of modern horse industry in future.