Miracle-dz/UniFAR-FTUs huggingface dataset:
Worldwide long-term trends in the incidence of nonalcoholic fatty liver disease during 1990–2019: A joinpoint and age-period-cohort analysis

Background Non-alcoholic fatty liver disease (NAFLD) was previously a neglected disease that is now becoming a worldwide pandemic. A better understanding of its incidence and long-term trends will help to increase public awareness of the disease and the development of future prevention strategies. Methods The incidence rates of NAFLD during 1990–2019 were collected from the Global Burden of Disease Study 2019 database according to the following parameters: sex, age, socio-demographic index, and geographical region. Estimated annual percentage changes and joinpoint models were used to assess the long-term trend of NAFLD, and an age-period-cohort model was used to assess the extents of the age, period, and cohort effects. Results Adult males, postmenopausal females, Latin American populations, and people in developing countries had a high risk of developing NAFLD. The joinpoint model indicated a new trend of increasing NAFLD incidence in 2005. Age was a risk factor affecting NAFLD incidence, with this effect increasing in more-recent periods. Younger birth cohorts had lower risks of NAFLD. Conclusions Recent prevention measures for NAFLD have achieved good initial results. However, it remains a high priority to increase the public awareness of this condition, develop its diagnostic criteria, identify cost-effective screening methods, and seek policy support to act against NAFLD, which will be a major public health problem in the future.
A variable gene family encoding nodule-specific cysteine-rich peptides in pea (Pisum sativum L.)

Various legume plants form root nodules in which symbiotic bacteria (rhizobia) fix atmospheric nitrogen after differentiation into a symbiotic form named bacteroids. In some legume species, bacteroid differentiation is promoted by defensin-like nodule-specific cysteine-rich (NCR) peptides. NCR peptides have best been studied in the model legume Medicago truncatula Gaertn. , while in many other legumes relevant information is still fragmentary. Here, we characterize the NCR gene family in pea (Pisum sativum L.) using genomic and transcriptomic data. We found 360 genes encoding NCR peptides that are expressed in nodules. The sequences of pea NCR genes and putative peptides are highly variable and differ significantly from NCR sequences of M. truncatula. Indeed, only one pair of orthologs (PsNCR47–MtNCR312) has been identified. The NCR genes in the pea genome are located in clusters, and the expression patterns of NCR genes from one cluster tend to be similar. These data support the idea of independent evolution of NCR genes by duplication and diversification in related legume species. We also described spatiotemporal expression profiles of NCRs and identified specific transcription factor (TF) binding sites in promoters of “early” and “late” NCR genes. Further, we studied the expression of NCR genes in nodules of Fix– mutants and predicted potential regulators of NCR gene expression, one among them being the TF ERN1 involved in the early steps of nodule organogenesis. In general, this study contributes to understanding the functions of NCRs in legume nodules and contributes to understanding the diversity and potential antibiotic properties of pea nodule-specific antimicrobial molecules.
Exploring the RNase A scaffold to combine catalytic and antimicrobial activities. Structural characterization of RNase 3/1 chimeras

Design of novel antibiotics to fight antimicrobial resistance is one of the first global health priorities. Novel protein-based strategies come out as alternative therapies. Based on the structure-function knowledge of the RNase A superfamily we have engineered a chimera that combines RNase 1 highest catalytic activity with RNase 3 unique antipathogen properties. A first construct (RNase 3/1-v1) was successfully designed with a catalytic activity 40-fold higher than RNase 3, but alas in detriment of its anti-pathogenic activity. Next, two new versions of the original chimeric protein were created showing improvement in the antimicrobial activity. Both second generation versions (RNases 3/1-v2 and -v3) incorporated a loop characteristic of RNase 3 (L7), associated to antimicrobial activity. Last, removal of an RNase 1 flexible loop (L1) in the third version enhanced its antimicrobial properties and catalytic efficiency. Here we solved the 3D structures of the three chimeras at atomic resolution by X-ray crystallography. Structural analysis outlined the key functional regions. Prediction by molecular docking of the protein chimera in complex with dinucleotides highlighted the contribution of the C-terminal region to shape the substrate binding cavity and determine the base selectivity and catalytic efficiency. Nonetheless, the structures that incorporated the key features related to RNase 3 antimicrobial activity retained the overall RNase 1 active site conformation together with the essential structural elements for binding to the human ribonuclease inhibitor (RNHI), ensuring non-cytotoxicity. Results will guide us in the design of the best RNase pharmacophore for anti-infective therapies.
The current status of old traditional medicine introduced from Persia to China

Traditional Chinese medicine (TCM) includes over ten thousand herbal medicines, some of which were introduced from outside countries and territories. The Silk Road enabled the exchange of merchandise such as teas, silks, carpets, and medicines between the East and West of the Eurasia continent. During this time, the ‘Compendium of Materia Medica’ (CMM) was composed by a traditional medicine practitioner, Shizhen Li (1,518–1,593) of the Ming Dynasty. This epoch-making masterpiece collected knowledge of traditional medical materials and treatments in China from the 16th century and before in utmost detail, including the origin where a material was obtained. Of 1892 medical materials from the CMM, 46 came from Persia (now Iran). In this study, the basic information of these 46 materials, including the time of introduction, the medicinal value in TCM theory, together with the current status of these medicines in China and Iran, are summarized. It is found that 20 herbs and four stones out of the 46 materials are registered as medicinal materials in the latest China Pharmacopoeia. Now most of these herbs and stones are distributed in China or replacements are available but saffron, ferula, myrrh, and olibanum are still highly dependent on imports. This study may contribute to the further development, exchange, and internationalization of traditional medicine of various backgrounds in the world, given the barriers of transportation and language are largely eased in nowadays.
Epidemiological characteristics and molecular evolution mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP), a type of Klebsiella pneumoniae (KP) that exhibits hypervirulence and carbapenem resistance phenotypes, can cause severe infections, both hospital- and community-acquired infections. CR-hvKP has brought great challenges to global public health and is associated with significant morbidity and mortality. There are many mechanisms responsible for the evolution of the hypervirulence and carbapenem resistance phenotypes, such as the horizontal transfer of the plasmid carrying the carbapenem resistance gene to hypervirulent Klebsiella pneumoniae (hvKP) or carbapenemase-producing Klebsiella pneumoniae (CRKP) acquiring a hypervirulence plasmid carrying a virulence-encoding gene. Notably, KP can evolve into CR-hvKP by acquiring a hybrid plasmid carrying both the carbapenem resistance and hypervirulence genes. In this review, we summarize the evolutionary mechanisms of resistance and plasmid-borne virulence as well as the prevalence of CR-hvKP.
The water–energy nexus in irrigated agriculture in South Asia: Critical hotspots of irrigation water use, related energy application, and greenhouse gas emissions for wheat, rice, sugarcane, and cotton in Pakistan

Asia has a large water scarcity problem, especially in countries depending on irrigation, limiting agricultural production, and increasing food insecurity. When water becomes scarce, it needs conveyance over longer distances or pumping from deeper groundwater stocks, requiring pumping energy, often fossil energy, emitting greenhouse gasses. This causes a trade-off between irrigation water supply and fossil energy use contributing to global warming. This research focuses on the water–energy–food nexus in irrigated agriculture to improve resource management. It uses Pakistan as its case study area and assesses water consumption, energy (EFs), and carbon footprints (CFs) associated with irrigation water supply for the major crops (wheat, rice, sugarcane, and cotton) per district. The method first assesses irrigation water volumes (surface and groundwater) per crop per district and next the energy and CO2 emissions to provide this water. Data on allocated water volumes, crop areas and pumping types were taken from governmental reports. Groundwater tables and energy data were taken from scientific publication based also on actual measurements. The research identifies unfavorable hotspots and favorable areas from a water and energy perspective. Drivers determining water consumption, EFs, and CFs related to irrigation water supply show spatial and temporal differences and include crop types, temporal crop water requirements, fractions of gravity-fed and pumped water, groundwater tables, and energy sources (diesel, electric, and solar). In Pakistan, annual irrigation supply requires 103 PJ of energy generating a CF of 11 109 kg CO2 (6% of the national CF). Diesel pumps, pumping shallow groundwater, contribute most (73%), followed by electric pumps pumping deep groundwater. Energy for surface water pumping is negligible. Wheat contributes 31% to the EF, cotton 27%, and sugarcane and rice 21% each. CFs, caused by fossil energy use to pump irrigation water, are also dominated by wheat (32%) and cotton (31%), followed by rice and sugarcane (19% each). Ten hotspot districts contribute 42% to the EF of the major crops and increased by 21% in fourteen years. Wheat and cotton in Punjab and rice and cotton in Sindh are the most energy-intensive. EFs range between 3,500 and 5,000 TJ per district, with some districts in Punjab, the most important agricultural province, using even more. Large differences occur among EFs per unit of irrigation water, ranging between 7 and 2,260 KJ/m3, CFs between 1 and 444 g CO2/m3. The identification of hotspots may contribute to measures to minimize water consumption, EFs and CFs for agriculture in Pakistan. Other countries that also rely on irrigation could apply methods applied here to identify hotspots. Graphical Abstract Irrigation water supply, related energy and greenhouse gas emissions major crops Pakistan.
4-1BB: A promising target for cancer immunotherapy

Immunotherapy, powered by its relative efficacy and safety, has become a prominent therapeutic strategy utilized in the treatment of a wide range of diseases, including cancer. Within this class of therapeutics, there is a variety of drug types such as immune checkpoint blockade therapies, vaccines, and T cell transfer therapies that serve the purpose of harnessing the body’s immune system to combat disease. Of these different types, immune checkpoint blockades that target coinhibitory receptors, which dampen the body’s immune response, have been widely studied and established in clinic. In contrast, however, there remains room for the development and improvement of therapeutics that target costimulatory receptors and enhance the immune response against tumors, one of which being the 4-1BB (CD137/ILA/TNFRSF9) receptor. 4-1BB has been garnering attention as a promising therapeutic target in the setting of cancer, amongst other diseases, due to its broad expression profile and ability to stimulate various signaling pathways involved in the generation of a potent immune response. Since its discovery and demonstration of potential as a clinical target, major progress has been made in the knowledge of 4-1BB and the development of clinical therapeutics that target it. Thus, we seek to summarize and provide a comprehensive update and outlook on those advancements in the context of cancer and immunotherapy.
The monocyte-to-osteoclast transition in rheumatoid arthritis: Recent findings

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation leading to joint destruction and deformity. The crucial role of osteoclasts in the bone erosion in RA has been demonstrated. Deregulated osteoclastogenesis which is affected by environmental factors including the inflammatory state, as well as genetic and epigenetic factors, is one of hallmarks of RA pathogenesis. An enhanced-monocyte-to-osteoclast transition plays an important role in osteoclast upregulation in RA because under specific stimuli, circulating monocytes might migrate to a specific location in the bones and fuse with each other to become mature multinucleated osteoclasts. To understand the mechanism of bone damage in RA and to develop novel treatments targeting osteoclast upregulation, it is important to clarify our understanding of the monocyte-to-osteoclast transition in RA. Several potential targets which inhibit both inflammation and osteoclastogenesis, as well as regulators that affect the monocyte-to-osteoclast transition have been revealed by recent studies. Here, we review the factors affecting osteoclastogenesis in RA, summarize the anti-osteoclastogenic effects of current RA treatments, and identify promising therapeutic targets relating to both inflammation and osteoclastogenesis.
Editorial: Emerging non-volatile memories and beyond: From fundamental physics to applications

At the beginning of the 21st century, many scientists and engineers from the most important semiconductor industries began to question whether, and to which extent, the NAND memory technology could be further scaled or not. Due to the widespread exploitation of NAND memories in electronic devices, this debate became soon a hot topic. While the mainstream NAND technology relies on charge trapping and floating gates, broadly speaking the alternative technologies rely instead on the possibility to alter the state of a material as the means to store the information, the device physics and physical structure being unique to each technology. All these technologies (phase change memories [1], resistive RAMs [2], spin-transfer-torque RAMs [3], ferroelectric memories [4], and others) were collectively addressed to as Emerging Non-Volatile Memories. At the International Electron Devices Meeting IEDM 2012, the attendants to the panel session Will Future Non-Volatile-Memory Contenders Disrupt NAND? were asked to vote which technology in their opinion would have taken the lead in the next decade. The majority of the votes were cast to the NAND technology, that was indicated as the successor of itself; and among the emerging technologies, phase change memories were on top of the list closely followed by resistive RAMs. As a matter of fact, the manufacturing understanding of the alternative technologies was largely immature, the fabrication costs were substantially higher, and the long-term behavior was not well evaluated and established as that of the NAND technology. The predominance of phase change memories as a possible replacement for NAND derived from the deeper investigation of such a technology, that was started by the pioneering and visionary work of Ovshinskiy in the 1960s. In the late 2000s only phase change memories had in fact been commercially exploited by Numonyx aiming OPEN ACCESS
Genome-wide characterization of ovate family protein gene family associated with number of seeds per silique in Brassica napus

Ovate family proteins (OFPs) were firstly identified in tomato as proteins controlling the pear shape of the fruit. Subsequent studies have successively proved that OFPs are a class of negative regulators of plant development, and are involved in the regulation of complex traits in different plants. However, there has been no report about the functions of OFPs in rapeseed growth to date. Here, we identified the OFPs in rapeseed at the genomic level. As a result, a total of 67 members were obtained. We then analyzed the evolution from Arabidopsis thaliana to Brassica napus, illustrated their phylogenetic and syntenic relationships, and compared the gene structure and conserved domains between different copies. We also analyzed their expression patterns in rapeseed, and found significant differences in the expression of different members and in different tissues. Additionally, we performed a GWAS for the number of seeds per silique (NSPS) in a rapeseed population consisting of 204 natural accessions, and identified a new gene BnOFP13_2 significantly associated with NSPS, which was identified as a novel function of OFPs. Haplotype analysis revealed that the accessions with haplotype 3 had a higher NSPS than other accessions, suggesting that BnOFP13_2 is associated with NSPS. Transcript profiling during the five stages of silique development demonstrated that BnOFP13_2 negatively regulates NSPS. These findings provide evidence for functional diversity of OFP gene family and important implications for oilseed rape breeding.
The effects of fermented pineapple residue on growth performance, meat quality, and rumen microbiota of fattening Simmental bull

In this study, silage Pennisetum sinese Roxb-based diet was replaced with fermented pineapple residue (FPR) at the replacement ratio of 0% (CON), 25% (T25), and 50% (T50) in fattening Simmental bulls for 30 days to evaluate the effects of FPR on growth performance, serum indexes, and ruminal characteristics. A total of 30 Simmental bulls (546 ± 44 kg initial BW) were allocated to three groups according to a completely randomized design. On day 30, the slaughter performance and meat quality were determined. Rumen fluids were collected for analyzing the rumen fermentation parameters and microbiota composition on day 30. The results showed that the average daily weight gain increased (P < 0.05) as the proportion of FPR rose. Within treatments, the T25 group reached more profit (5.34 RMB per day per bull) than CON while T50 was 3.69. The content of crude fat, cysteine, and proline in the muscle of T50 increased significantly (P < 0.05). The amounts of tyrosine, proline, and phenylalanine were significantly increased in the T25 (P < 0.05). The beta diversity analysis showed significant differences among the rumen bacterial flora of each group (P < 0.05). In the T25 group, the relative abundance of Spirochaetes decreased significantly (P < 0.05). The relative abundance of Lachnospiraceae_bacterium_RM44 was significantly lower (P < 0.05). Thus, FPR could improve the growth performance, economic benefits, and meat quality without adverse effects on ruminal characteristics.
The mediation and interaction of depressive symptoms in activities of daily living and active aging in rural elderly: A cross-sectional survey

Background Compared with urban areas, old adults in rural areas have limited access to medical and health resources in China. Active of daily living ability (ADL) decline and depressive symptoms are common in rural older adults. In particular, the depressive symptoms of the elderly in rural areas are often ignored. Thus, it is difficult to realize high-level active aging at the individual level. In order to explore the effects of ADL and depressive symptoms on the active aging of rural elderly, we conducted a survey and analyzed the mediation and interaction effects of depressive symptoms of ADL on active aging. Methods From July to November 2019, a cross-sectional study of 945 elderly rural individuals was conducted in three townships in Xiangtan County, China. Active aging, ADL, and depressive symptoms were assessed using the positive aging questionnaire (PAEQ), ADL scale, and depression in old age scale (DIA-S), respectively. PROCESS macro program model 4 and logistic regression were used to explore the mediation and interaction between ADL and depressive symptoms on active aging. Results The proportions of rural elderly with an active aging level were 23.5% (well above average), 50.9% (above average), 24.1% (below average), 1.5% (well below average), respectively. The rates of ADL decline and depressive symptoms were 44.7 and 19.7%, respectively. Mediated effect analysis showed that the relationship between ADL and active aging could be partly mediated by depressive symptoms (ab = −0.2382, boot SE = 0.0437), and the 95% confidence interval was [−0.3311, −0.1584]. The mediating effect proportion of the total effect was 30.7%. Logistic regression showed that ADL and depressive symptoms have an interactive additive effect on active aging. The relative excess risk of interaction (RERI), the attributable proportion due to interaction (API), and the synergy index (SI) scores were 13.109, 0.621, and 2.871, respectively. Older adults with ADL decline and depressive symptoms had higher (OR = 21.115) odds of well-below-average active aging compared with older adults with ADL decline (OR = 3.258) or only depressive symptoms (OR = 5.749). Conclusion The findings suggest that the association between ADL and active aging is persistent and partly mediated by depressive symptoms, and comorbid depressive symptoms and ADL decline have an additive effect on active aging. Maintaining independence is an important factor for realizing active aging. However, for the rural elderly with ADL decline and low-level active aging, we can promote the realization of high-level active aging at the individual level through the prevention and treatment of depressive symptoms based on multidisciplinary care.
How sphingolipids affect T cells in the resolution of inflammation

The concept of proper resolution of inflammation rather than counteracting it, gained a lot of attention in the past few years. Re-assembly of tissue and cell homeostasis as well as establishment of adaptive immunity after inflammatory processes are the key events of resolution. Neutrophiles and macrophages are well described as promotors of resolution, but the role of T cells is poorly reviewed. It is also broadly known that sphingolipids and their imbalance influence membrane fluidity and cell signalling pathways resulting in inflammation associated diseases like inflammatory bowel disease (IBD), atherosclerosis or diabetes. In this review we highlight the role of sphingolipids in T cells in the context of resolution of inflammation to create an insight into new possible therapeutical approaches.
Innate immune evasion by alphaviruses

Alphaviruses contain many human and animal pathogens, such as CHIKV, SINV, and VEEV. Accumulating evidence indicates that innate immunity plays an important role in response to alphaviruses infection. In parallel, alphaviruses have evolved many strategies to evade host antiviral innate immunity. In the current review, we focus on the underlying mechanisms employed by alphaviruses to evade cGAS-STING, IFN, transcriptional host shutoff, translational host shutoff, and RNAi. Dissecting the detailed antiviral immune evasion mechanisms by alphaviruses will enhance our understanding of the pathogenesis of alphaviruses and may provide more effective strategies to control alphaviruses infection.