Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice.

BACKGROUND: Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled. METHODS: To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit. RESULTS: Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy. CONCLUSION: The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.

Primary care providers' preferences for pay-for-performance programs: a discrete choice experiment study in Shandong China.

BACKGROUND: Pay-for-performance (P4P) schemes are commonly used to incentivize primary healthcare (PHC) providers to improve the quality of care they deliver. However, the effectiveness of P4P schemes can vary depending on their design. In this study, we aimed to investigate the preferences of PHC providers for participating in P4P programs in a city in Shandong province, China. METHOD: We conducted a discrete choice experiment (DCE) with 882 PHC providers, using six attributes: type of incentive, whom to incentivize, frequency of incentive, size of incentive, the domain of performance measurement, and release of performance results. Mixed logit models and latent class models were used for the statistical analyses. RESULTS: Our results showed that PHC providers had a strong negative preference for fines compared to bonuses (- 1.91; 95%CI - 2.13 to - 1.69) and for annual incentive payments compared to monthly (- 1.37; 95%CI - 1.59 to - 1.14). Providers also showed negative preferences for incentive size of 60% of monthly income, group incentives, and non-release of performance results. On the other hand, an incentive size of 20% of monthly income and including quality of care in performance measures were preferred. We identified four distinct classes of providers with different preferences for P4P schemes. Class 2 and Class 3 valued most of the attributes differently, while Class 1 and Class 4 had a relatively small influence from most attributes. CONCLUSION: P4P schemes that offer bonuses rather than fines, monthly rather than annual payments, incentive size of 20% of monthly income, paid to individuals, including quality of care in performance measures, and release of performance results are likely to be more effective in improving PHC performance. Our findings also highlight the importance of considering preference heterogeneity when designing P4P schemes.

Expert consensus on Prospective Precision Diagnosis and Treatment Strategies for Osteoporotic Fractures.

Osteoporotic fractures are the most severe complications of osteoporosis, characterized by poor bone quality, difficult realignment and fixation, slow fracture healing, and a high risk of recurrence. Clinically managing these fractures is relatively challenging, and in the context of rapid aging, they pose significant social hazards. The rapid advancement of disciplines such as biophysics and biochemistry brings new opportunities for future medical diagnosis and treatment. However, there has been limited attention to precision diagnosis and treatment strategies for osteoporotic fractures both domestically and internationally. In response to this, the Chinese Medical Association Orthopaedic Branch Youth Osteoporosis Group, Chinese Geriatrics Society Geriatric Orthopaedics Committee, Chinese Medical Doctor Association Orthopaedic Physicians Branch Youth Committee Osteoporosis Group, and Shanghai Association of Integrated Traditional Chinese and Western Medicine Osteoporosis Professional Committee have collaborated to develop this consensus. It aims to elucidate emerging technologies that may play a pivotal role in both diagnosis and treatment, advocating for clinicians to embrace interdisciplinary approaches and incorporate these new technologies into their practice. Ultimately, the goal is to improve the prognosis and quality of life for elderly patients with osteoporotic fractures.

Reinstatement of the fission yeast species Schizosaccharomyces versatilis Wickerham et Duprat, a sibling species of Schizosaccharomyces japonicus.

Schizosaccharomyces japonicus Yukawa et Maki (1931) and Schizosaccharomyces versatilis Wickerham et Duprat (1945) have been treated as varieties of S. japonicus or as conspecific, based on various approaches including mating trials and nDNA/nDNA optical reassociation studies. However, the type strains of S. japonicus and S. versatilis differ by five substitutions (99.15% identity) and one 1-bp indel in the sequences of the D1/D2 domain of the 26S rRNA gene, and 23 substitutions (96.3% identity) and 31-bp indels in the sequences of internal transcribed spacer (ITS) of rRNA, suggesting that they may not be conspecific. To reassess their taxonomic status, we conducted mating trials and whole-genome analyses. Mating trials using the type strains showed a strong but incomplete prezygotic sterility barrier, yielding interspecies mating products at two orders of magnitude lower efficiency than intraspecies matings. These mating products, which were exclusively allodiploid hybrids, were unable to undergo the haplontic life cycle of the parents. We generated chromosome-level gap-less genome assemblies for both type strains. Whole genome sequences yielded an average nucleotide identity (ANI) of 86.4%, indicating clear separation of S. japonicus and S. versatilis. Based on these findings, we propose the reinstatement of S. versatilis as a distinct species (holotype strain: CBS 103T and ex-types: NRRL Y-1026, NBRC 1607, ATCC 9987, PYCC 7100; Mycobank no.: 847838).

A Factor-Free Hydrogel with ROS Scavenging and Responsive Degradation for Enhanced Diabetic Bone Healing.

In view of the increased levels of reactive oxygen species (ROS) that disturb the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), the repair of diabetic bone defects remains a great challenge. Herein, a factor-free hydrogel is reported with ROS scavenging and responsive degradation properties for enhanced diabetic bone healing. These hydrogels contain ROS-cleavable thioketal (TK) linkers and ultraviolet (UV)-responsive norbornene (NB) groups conjugated with 8-arm PEG macromers, which are formed via UV crosslinking-mediated gelation. Upon reacting with high levels of ROS in the bone defect microenvironment, ROS-cleavable TK linkers are destroyed, allowing the responsive degradation of hydrogels, which promotes the migration of BMSCs. Moreover, ROS levels are reduced through hydrogel-mediated ROS scavenging to reverse BMSC differentiation from adipogenic to osteogenic phenotype. As such, a favorable microenvironment is created after simultaneous ROS scavenging and hydrogel degradation, leading to the effective repair of bone defects in diabetic mouse models, even without the addition of growth factors. Thus, this study presents a responsive hydrogel platform that regulates ROS scavenging and stromal degradation in bone engineering.

Articular cartilage repair biomaterials: strategies and applications.

Articular cartilage injury is a frequent worldwide disease, while effective treatment is urgently needed. Due to lack of blood vessels and nerves, the ability of cartilage to self-repair is limited. Despite the availability of various clinical treatments, unfavorable prognoses and complications remain prevalent. However, the advent of tissue engineering and regenerative medicine has generated considerable interests in using biomaterials for articular cartilage repair. Nevertheless, there remains a notable scarcity of comprehensive reviews that provide an in-depth exploration of the various strategies and applications. Herein, we present an overview of the primary biomaterials and bioactive substances from the tissue engineering perspective to repair articular cartilage. The strategies include regeneration, substitution, and immunization. We comprehensively delineate the influence of mechanically supportive scaffolds on cellular behavior, shedding light on emerging scaffold technologies, including stimuli-responsive smart scaffolds, 3D-printed scaffolds, and cartilage bionic scaffolds. Biologically active substances, including bioactive factors, stem cells, extracellular vesicles (EVs), and cartilage organoids, are elucidated for their roles in regulating the activity of chondrocytes. Furthermore, the composite bioactive scaffolds produced industrially to put into clinical use, are also explicitly presented. This review offers innovative solutions for treating articular cartilage ailments and emphasizes the potential of biomaterials for articular cartilage repair in clinical translation.

Organoid assessment technologies.

Despite enormous advances in the generation of organoids, robust and stable protocols of organoids are still a major challenge to researchers. Research for assessing structures of organoids and the evaluations of their functions on in vitro or in vivo is often limited by precision strategies. A growing interest in assessing organoids has arisen, aimed at standardizing the process of obtaining organoids to accurately resemble human-derived tissue. The complex microenvironment of organoids, intricate cellular crosstalk, organ-specific architectures and further complicate functions urgently quest for high-through schemes. By utilizing multi-omics analysis and single-cell analysis, cell-cell interaction mechanisms can be deciphered, and their structures can be investigated in a detailed view by histological analysis. In this review, we will conclude the novel approaches to study the molecular mechanism and cell heterogeneity of organoids and discuss the histological and morphological similarity of organoids in comparison to the human body. Future perspectives on functional analysis will be developed and the organoids will become mature models.

Exploring the association of PM2.5 with lung cancer incidence under different climate zones and socioeconomic conditions from 2006 to 2016 in China.

Air pollution generated by urbanization and industrialization poses a significant negative impact on public health. Particularly, fine particulate matter (PM2.5) has become one of the leading causes of lung cancer mortality worldwide. The relationship between air pollutants and lung cancer has aroused global widespread concerns. Currently, the spatial agglomeration dynamic of lung cancer incidence (LCI) has been seldom discussed, and the spatial heterogeneity of lung cancer's influential factors has been ignored. Moreover, it is still unclear whether different socioeconomic levels and climate zones exhibit modification effects on the relationship between PM2.5 and LCI. In the present work, spatial autocorrelation was adopted to reveal the spatial aggregation dynamic of LCI, the emerging hot spot analysis was introduced to indicate the hot spot changes of LCI, and the geographically and temporally weighted regression (GTWR) model was used to determine the affecting factors of LCI and their spatial heterogeneity. Then, the modification effects of PM2.5 on the LCI under different socioeconomic levels and climatic zones were explored. Some findings were obtained. The LCI demonstrated a significant spatial autocorrelation, and the hot spots of LCI were mainly concentrated in eastern China. The affecting factors of LCI revealed an obvious spatial heterogeneity. PM2.5 concentration, nighttime light data, 2 m temperature, and 10 m u-component of wind represented significant positive effects on LCI, while education-related POI exhibited significant negative effects on LCI. The LCI in areas with low urbanization rates, low education levels, and extreme climate conditions was more easily affected by PM2.5 than in other areas. The results can provide a scientific basis for the prevention and control of lung cancer and related epidemics.

Engineered bacterial extracellular vesicles for central nervous system diseases.

The prevalence of central nervous system (CNS) diseases is on the rise as the population ages. The presence of various obstacles, particularly the blood-brain barrier (BBB), poses a challenge for drug delivery to the CNS. An expanding body of study suggests that gut microbiota (GM) plays an important role in CNS diseases. The communication between GM and CNS diseases has received increasing attention. Accumulating evidence indicates that the GM can modulate host signaling pathways to regulate distant organ functions by delivering bioactive substances to host cells via bacterial extracellular vesicles (BEVs). BEVs have emerged as a promising platform for the treatment of CNS diseases due to their nanostructure, ability to penetrate the BBB, as well as their low toxicity, high biocompatibility, ease of modification and large-scale culture. Here, we discuss the biogenesis, internalization mechanism and engineering modification methods of BEVs. We then focus on the use and potential role of BEVs in the treatment of CNS diseases. Finally, we outline the main challenges and future prospects for the application of BEVs in CNS diseases. We hope that the comprehensive understanding of the BEVs-based gut-brain axis will provide new insights into the treatment of CNS diseases.

RNF13 protects against pathological cardiac hypertrophy through p62-NRF2 pathway.

Heart failure (HF) severely impairs human health because of its high incidence and mortality. Cardiac hypertrophy is the main cause of HF, while its underlying mechanism is not fully clear. As an E3 ubiquitin ligase, Ring finger protein 13 (RNF13) plays a crucial role in many disorders, such as liver immune, neurological disease and tumorigenesis, whereas the function of RNF13 in cardiac hypertrophy remains largely unknown. In the present study, we found that the protein expression of RNF13 is up-regulated in the transverse aortic constriction (TAC)-induced murine hypertrophic hearts and phenylephrine (PE)-induced cardiomyocyte hypertrophy. Functional investigations indicated that RNF13 global knockout mice accelerates the degree of TAC-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis and heart dysfunction. On the contrary, adeno-associated virus 9 (AAV9) mediated-RNF13 overexpression mice alleviated cardiac hypertrophy. Furthermore, we demonstrated that adenoviral RNF13 attenuates the PE-induced cardiomyocyte hypertrophy and down-regulates the expression of cardiac hypertrophic markers, while the opposite results were observed in the RNF13 knockdown group. The RNA-sequence of RNF13 knockout and wild type mice showed that RNF13 deficiency activates oxidative stress after TAC surgery. In terms of the mechanism, we found that RNF13 directly interacted with p62 and promoted the activation of downstream NRF2/HO-1 signaling. Finally, we proved that p62 knockdown can reverse the effect of RNF13 in cardiac hypertrophy. In conclusion, RNF13 protects against the cardiac hypertrophy via p62-NRF2 axis.

Rasterizing CO2 emissions and characterizing their trends via an enhanced population-light index at multiple scales in China during 2013-2019.

Climate change caused by CO2 emissions (CE) has received widespread global concerns. Obtaining precision CE data is necessary for achieving carbon peak and carbon neutrality. Significant deficiencies of existing CE datasets such as coarse spatial resolution and low precision can hardly meet the actual requirements. An enhanced population-light index (RPNTL) was developed in this study, which integrates the Nighttime Light Digital Number (DN) Value from the National Polar-orbiting Partnership (NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) and population density to improve CE estimation accuracy. The CE from the Carbon Emission Accounts & Datasets (CEADS) was divided into three sectors, namely urban, industrial, and rural, to differentiate the heterogeneity of CE in each sector. The ordinary least square (OLS), geographically weighted regression (GWR), temporally weighted regression (TWR), and geographically and temporally weighted regression (GTWR) models were employed to establish the quantitative relationship between RPNTL and CE for each sector. The optimal model was determined through model comparison and precision evaluation and was utilized to rasterize CE for urban, industrial, and rural areas. Additionally, hot spot analysis, trend analysis, and standard deviation ellipses were introduced to demonstrate the spatiotemporal dynamic characteristics of CE at multiple scales. The performance of the GTWR outperformed other methods in estimating CE. The enhanced RPNTL demonstrated a higher coefficient of determination (R2 = 0.95) than the NTL (R2 = 0.92) in predicting CE, particularly in rural regions where the R2 value increased from 0.76 to 0.81. From 2013 to 2019, high CE was observed in eastern and northern China, while a decreasing trend was detected in northeastern China and Chengdu-Chongqing. Conversely, the Yangtze River Delta, Pearl River Delta, Fenwei Plain, and Henan Province showed an increasing trend. The center of gravity for industrial and rural CE is shifting towards western regions, whereas that for urban CE is moving northward. This study provides valuable insights for decision-making on CE control.

A review on the thermochemical treatments of biomass: Implications for hydrochar production and rare earth element recovery from hyperaccumulators.

Phytomining is a promising method that employs hyperaccumulators to concentrate metals from various substrates. Many studies on phytomining have been reported in the literature, while how to recover metals from hyperaccumulators has not been well resolved, which is critical for developing a complete phytomining-based metal recovery process. The most straightforward approach is to combust hyperaccumulators and recover metals from the combustion residue. However, the combustion process results in significant waste and carbon emissions. In contrast to combustion, thermochemical treatments can convert the biomass of hyperaccumulators to valuable products, such as biochar, hydrochar, biocrudes, and biogas. Therefore, it is more sustainable to develop a process that combines thermochemical treatments for metal recovery from hyperaccumulators. To achieve this objective, a systematic and comprehensive understanding of product characteristics and metal fate during thermochemical processing is required. In this article, three emerging thermochemical technologies, i.e., microwave-assisted pyrolysis, hydrothermal processing, and microwave-assisted hydrothermal treatment, are systematically reviewed in terms of conversion mechanisms, merits, demerits, product characteristics, and metal fate. Significant findings reported in the literature on the effects of operating parameters on product characteristics and metal fate during thermochemical treatment of waste biomass, especially those from hyperaccumulators, were summarized. Due to limited studies on thermochemical treatments of rare earth element hyperaccumulators, this review is expanded to include hyperaccumulators of any metal species. Based on comparisons among the three emerging thermochemical treatment technologies, microwave-assisted hydrothermal pyrolysis is identified as the most promising approach that favors carbon product obtainment and REE recovery from hyperaccumulators.

Can Brain Activities of Guided Metaphorical Restructuring Predict Therapeutic Changes?

The present study examined whether brain activities of metaphorical restructuring could predict improvements in emotion and general self-efficacy (GSES). Sixty-two anxious graduates were randomly assigned to either the metaphor group (n = 31) or the literal group (n = 31). After completing the pretest (T1), the participants were first presented with micro-counseling dialogues (MCD) to guide metaphorical or literal restructuring, and their functional brain activities were simultaneously recorded. They then completed the posttest (T2) and 1 week's follow-up (T3). It was found that (1) compared with the literal group, the metaphor group had more insightful experiences, a greater increase in positive affect and GSES at T2, and a greater decrease in psychological distress at T2 and T3; (2) the metaphor group showed a greater activation in the left inferior frontal gyrus (IFG) and bilateral temporal gyrus, and further activation in the left hippocampus positively predicted T2 GSES scores while that in the IFG and left hippocampus positively predicted the reduction slope of distress over the three time points. One important limitation is that the results should be interpreted with caution when generalizing to clinical anxiety samples due to the participants were graduate students with anxiety symptoms rather than clinical sample. These results indicated that metaphor restructuring produced greater symptom improvements, and activation in the hippocampus and IFG could predict these symptom improvements. This suggests that the activation of the two regions during the restructuring intervention may be a neural marker for symptom improvements.

Interleukin-21 knockout reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis.

Estrogen deficiency accelerates osteoporosis in elderly women. However, the role of IL-21 in postmenopausal osteoporosis remains unclear. Female wild-type (WT) C57BL/6 and IL-21 knockout (KO) mice were used for ovariectomy (OVX). Here, IL-21 levels were significantly increased in the serum and bone tissues of WT-OVX mice. The trabecular bone space of the femur was significantly increased, and the bone mass was reduced in OVX mice, accompanied by a significant decrease in the maximum load, energy absorption, and elastic modulus indices. In contrast, IL-21 knockout effectively alleviated the effects of OVX on bone mass. Serum TRACP-5b and receptor activator of nuclear factor kappa B ligand (RANKL) levels and osteoclastogenesis were significantly higher in OVX mice than in sham mice, while serum TRACP-5b and RANKL levels and osteoclastogenesis were significantly decreased in IL-21 KO + OVX mice compared to WT + OVX mice. IL-21 knockdown reduces TRACP-5b, RANKL, and osteoclastogenesis, effectively preventing bone resorption and alleviating the progression of OVX-induced osteoporosis.

Cell unit-inspired natural nano-based biomaterials as versatile building blocks for bone/cartilage regeneration.

The regeneration of weight-bearing bone defects and critical-sized cartilage defects remains a significant challenge. A wide range of nano-biomaterials are available for the treatment of bone/cartilage defects. However, their poor compatibility and biodegradability pose challenges to the practical applications of these nano-based biomaterials. Natural biomaterials inspired by the cell units (e.g., nucleic acids and proteins), have gained increasing attention in recent decades due to their versatile functionality, compatibility, biodegradability, and great potential for modification, combination, and hybridization. In the field of bone/cartilage regeneration, natural nano-based biomaterials have presented an unparalleled role in providing optimal cues and microenvironments for cell growth and differentiation. In this review, we systematically summarize the versatile building blocks inspired by the cell unit used as natural nano-based biomaterials in bone/cartilage regeneration, including nucleic acids, proteins, carbohydrates, lipids, and membranes. In addition, the opportunities and challenges of natural nano-based biomaterials for the future use of bone/cartilage regeneration are discussed.

Supramolecular assemblies with spatio-temporal sequential drug delivery capability treat spinal cord injury via neuroprotection and immunoregulation.

Spinal cord injury (SCI) can result in irreversible motor and sensory deficits. However, up to data, clinical first-line drugs have ambiguous benefits and debilitating side effects, mainly due to the insufficient accumulation, poor physiological barrier penetration, and lack of spatio-temporal controlled release at lesion tissue. Herein, we proposed a supramolecular assemblies composed of hyperbranched polymer-formed core/shell structure through host-guest interactions. Such HPAA-BM@CD-HPG-C assemblies co-loaded with p38 inhibitor (SB203580) and insulin-like growth factor 1(IGF-1) are able to achieve time- and space-programmed sequential delivery benefiting from their cascaded responsiveness. The core-shell disassembly of HPAA-BM@CD-HPG-C occurs in acidic micro-environment around lesion, achieving preferentially the burst release of IGF-1 to protect survival neurons. Subsequently, the HPAA-BM cores containing SB203580 are endocytosed by the recruited macrophages and degraded by intracellular GSH, accelerating the release of SB203580 to promote the conversion from M1 to M2 macrophage. Hence, the successive synergy of neuroprotection and immunoregulation effects contribute to subsequent nerve repair and locomotor recovery as demonstrated in vitro and in vivo studies. Thus, our fabrication provides a strategy that multiple drugs co-delivery in a spatio-temporal selective manner adapting to the disease progression through self-cascaded disintegration, are expected to realize multidimensional precise treatment of SCI.

A comprehensive review on the ultrasound-enhanced leaching recovery of valuable metals: Applications, mechanisms and prospects.

In recent two decades, ultrasound has been broadly applied to the hydrometallurgical leaching process to recover valuable metals within raw materials, aiming to solve the shortcomings of the conventional leaching process, including relatively low leaching recovery, long leaching duration, high reagent usage, high energy consumption and so on. The present work focuses on a comprehensive overview of the ultrasound-enhanced leaching of various metals, such as common nonferrous and ferrous metals, rare metals, rare earth elements, and precious metals, from raw metal ores and secondary resources. Moreover, the enhanced leaching mechanisms by ultrasound are discussed in detail and summarized based on the improvement of leaching kinetics, enhancement of the mass transfer and diffusion of lixiviants, and promotion of the oxidative conversion of metals from insoluble to soluble states. Lastly, the challenges and outlooks of future research on the leaching recovery for valuable metals with the assistance of ultrasound irradiation are proposed.

Endothelial Stat3 activation promotes osteoarthritis development.

The mechanism of the balance between subchondral angiogenesis and articular damage within osteoarthritis (OA) progression remains a mystery. However, the lack of specific drugs leads to limited clinical treatment options for OA, frequently failing to prevent eventual joint destruction in patients. Increasing evidence suggests that subchondral bone angiogenesis precedes cartilage injury, while proliferating endothelial cells (ECs) induce abnormal bone formation. Signal transducer and activator of transcription 3 (Stat3) is triggered by multiple cytokines in the OA microenvironment. Here, we observed elevated Stat3 activation in subchondral bone H-type vessels. Endothelial Stat3 activation will lead to stronger cell proliferation, migration and angiogenesis by simulating ECs in OA. In contrast, either Stat3 activation inhibition or knockdown of Stat3 expression could relieve such alterations. More interestingly, blocking Stat3 in ECs alleviated angiogenesis-mediated osteogenic differentiation and chondrocyte lesions. Stat3 inhibitor reversed surgically induced subchondral bone H-type vessel hyperplasia in vivo, significantly downregulating vessel volume and vessel number. Due to the reduced angiogenesis, subchondral bone deterioration and cartilage loss were alleviated. Overall, our data suggest that endothelial Stat3 activation is an essential trigger for OA development. Therefore, targeted Stat3 blockade is a novel promising therapeutic regimen for OA.

Long-term outcomes of drug-coated balloon treatment of calcified coronary artery lesions: a multicenter, retrospective, propensity matching study.

Background: Coronary artery calcification (CAC) is associated with high rates of restenosis and adverse clinical events after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Objectives: The aim of this study was to evaluate the long-term clinical outcomes of drug-coated balloon (DCB)-only treatment for de novo lesions with and without CAC. Methods: Patients with de novo coronary disease treated with the DCB-only strategy were retrospectively enrolled from three centers and categorized into a CAC group and a non-CAC group. The primary endpoint was the target lesion failure (TLF) rate during the 3-year follow-up. Secondary endpoints included the occurrence of major adverse cardiac events (MACEs), target lesion revascularization (TLR), cardiac death, myocardial infarction (MI) and any revascularization. Propensity score matching (PSM) was conducted to assemble a cohort of patients with similar baseline characteristics. Results: A total of 1,263 patients with 1,392 lesions were included, and 243 patients were included in each group after PSM. Compared with the non-CAC group, the incidence rates of TLF (9.52% vs. 4.94%, odds ratio [OR]: 2.080; 95% confidence interval [CI]: 1.083-3.998, P = 0.034) and TLR (7.41% vs. 2.88%, OR: 2.642; 95% CI: 1.206-5.787, P = 0.020) in the CAC group were higher. The incidence rates of MACE (12.35% vs. 7.82%, OR: 1.665; 95% CI: 0.951-2.916, P = 0.079), cardiac death (2.06% vs. 2.06%, OR: 0.995; 95% CI: 0.288-3.436, P = 0.993), MI (1.23% vs. 0.82%, OR: 2.505; 95% CI: 0.261-8.689, P = 0.652) and any revascularization (12.76% vs. 9.67%, OR: 1.256; 95% CI: 0.747-2.111, P = 0.738) were similar between groups. Conclusions: CAC increased the incidence of TLF and TLR without a substantial increase in the risk of MACE, cardiac death, MI, or any revascularization in patients treated with DCB-only angioplasty during the 3-year follow-up.

Population transcriptomics uncover the relative roles of positive selection and differential expression in Batrachium bungei adaptation to the Qinghai-Tibetan plateau.

KEY MESSAGE: Positive selection genes are related to metabolism, while differentially expressed genes are related to photosynthesis, suggesting that genetic adaptation and expression regulation may play independent roles in different gene classes. Genome-wide investigation of the molecular mechanisms for high-altitude adaptation is an intriguing topic in evolutionary biology. The Qinghai-Tibet Plateau (QTP) with its extremely variable environments is an ideal site for studying high-altitude adaptation. Here, we used transcriptome data of 100 individuals from 20 populations collected from various altitudes on the QTP to investigate the adaptive mechanisms of the aquatic plant Batrachium bungei at both the genetic and transcriptional level. To explore genes and biological pathways that may contribute to QTP adaptation, we employed a two-step approach, in which we identified positively selected genes and differentially expressed genes using the landscape genomic and differential expression approaches. The positive selection analysis showed that genes involved in metabolic regulation played a crucial role in B. bungei adaptation to the extreme environments of the QTP, especially intense ultraviolet radiation. Altitude-based differential expression analysis suggested that B. bungei could increase the rate of energy dissipation or reduce the efficiency of light energy absorption by down regulating the expression of photosynthesis-related genes to adapt to the strong ultraviolet radiation. Weighted gene co-expression network analysis identified ribosomal genes as hubs of altitude adaptation in B. bungei. Only a small part of genes (about 10%) overlapped between positively selected genes and differentially expressed genes in B. bungei, suggesting that genetic adaptation and gene expression regulation might play relatively independent roles in different categories of functional genes. Taken together, this study enriches our understanding of the high-altitude adaptation mechanism of B. bungei on the QTP.