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Selenium (Se) is a beneficial element for plant growth and development. In this study, three-year-old potted 'Qingcui' plums were treated with Na2SeO4 (Se6+) or selenomethionine (SeMet Se2-) to explore the effect of Se on the plant growth, fruit quality, and 5-hydroxytryptophan (5-HTP) metabolism. Flower and fruit numbers, fruit quality and yield, Se content, and 5-HTP metabolites and enzymes were detected. The results showed that the flower and fruit numbers, and yield were significantly increased by the Se application. There were no significant differences in the fruit diameters, fruit mass, edible part ratio, titratable acids, water content, and solid acid ratio among the treatments. The total soluble solids, soluble protein, and malondialdehyde contents under the Se6+ treatment showed no significant difference compared to the Se2- treatment, but they were significantly higher than these under control by 16.71%, 39.13%, and 36.27%, respectively. The Se application markedly increased plant the Se content, and Se contents in the roots and leaves, or the fruits were significantly larger by the Se6+ treatments than the Se2- treatment. The leaves' pigment contents under the Se2- treatments were significantly larger than those under the control or Se6+ treatment. Tryptophan was not significantly influenced, the 5-HTP and 5-methoxytryptophan contents were reduced in the roots, and increased in the leaves, and the serotonin content was only significantly increased in the roots by the Se treatments. The tryptophan hydroxylase and hydroxyindole-O-methyltransferase levels were slightly influenced, and the tryptophan decarboxylase level in the roots or fruits was significantly increased by the Se treatments. The Se application had beneficial effects on the plant growth, fruit quality, and Se content, especially in the Se6+ treatment, and influenced the 5-HTP metabolism.

This study aims to explore whether social media information overload affects medical staff's information avoidance behavior and the extent to which time pressure mediates and job performance moderates this relationship. We analyze survey data on 586 medical staff from 11 hospitals in China using bootstrapping. The results demonstrate that medical staff's social media information overload has a significant positive effect on their information avoidance behavior and that time pressure plays a partial mediating role. Additionally, job performance moderates the impact of social media information overload on information avoidance. Further, high-performing medical staff's social media information overload has a greater impact on their information avoidance behavior than that of medical staff with low job performance. This study satisfies the call for an in-depth investigation of social media information avoidance by uncovering the relationship between social media information overload and the job performance of medical staff. The findings not only shed light on intention from an informational overload perspective but also provide fresh insights for practitioners on how to strategically manage information overload. Medical staff are suggested to be aware of both the positive and the negative effects of social media on their work and life as well as secure the time to deal with social media information to benefit from the convenience that social media brings to their work and life spheres without spending too much time on social media, which negatively affects working time. Healthcare institution managers should avoid sending too much information to high-performing medical staff, as information overload may cause them to be more inclined to “hide from” this information in reality.

Energy performance contracting (EPC) as a market instrument has been effective in promoting energy efficiency worldwide, but it has encountered many insurmountable obstacles in rural energy management. In this study, based on the characteristics of energy management in rural areas, three EPC modes are designed and tested in 24,000 rural households. The test results show that two adapted EPC modes of local government involvement and energy payment directly from the national grid can effectively overcome the barriers encountered in the traditional EPC modes and work well under the economic and social environmental conditions in rural areas. The key to the adaptation of the traditional EPC modes is the introduction of the local government as the third party. Participation of the third party can effectively reduce and remove the barriers and risks and increase the mutual trust between the clients (households) and the energy service companies (ESCOs). Based on the testing results, this study suggests that governmental departments should formulate relevant EPC policies and technical guidelines within the rural context. This research recommends that farmers should not manage their energy services by themselves and it is suggested to out-contracting ESCOs by applying the modes developed and tested by this paper.

The periodic coronal rain and in-phase radiative intensity pulsations have been observed in multiple wavelengths in recent years. However, due to the lack of three-dimensional coronal magnetic fields and thermodynamic data in observations, it remains challenging to quantify the coronal heating rate that drives the mass cycles. In this work, based on the MURaM code, we conduct a three-dimensional radiative magnetohydrodynamic simulation spanning from the convective zone to the corona, where the solar atmosphere is heated self-consistently through dissipation resulting from magnetoconvection. For the first time, we model the periodic coronal rain in an active region. With a high spatial resolution, the simulation well resembles the observational features across different extreme-ultraviolet wavelengths. These include the realistic interweaving coronal loops, periodic coronal rain, and periodic intensity pulsations, with two periods of 3.0 hr and 3.7 hr identified within one loop system. Moreover, the simulation allows for a detailed three-dimensional depiction of coronal rain on small scales, revealing adjacent shower-like rain clumps ∼500 km in width and showcasing their multithermal internal structures. We further reveal that these periodic variations essentially reflect the cyclic energy evolution of the coronal loop under thermal nonequilibrium state. Importantly, as the driver of the mass circulation, the self-consistent coronal heating rate is considerably complex in time and space, with hour-level variations in 1 order of magnitude, minute-level bursts, and varying asymmetry reaching ten times between footpoints. This provides an instructive template for the ad hoc heating function and further enhances our understanding of the coronal heating process.

This article examines how a new form of preventative care provision—dancing with care (DWC)—promotes social inclusion among older women in China and explores whether DWC can be regarded as an effective way to address the challenges these older women face in improving their social inclusion and achieving a healthy lifestyle. Our study demonstrates that various dimensions of DWC play a vital role in addressing the difficulties these older women encounter in their struggle to end their own social exclusion: These dimensions include levels of happiness, social network involvement, access to social support in “preventative care terms”, and the role of own’s grandchildren as a means to social bonding. Various dimensions of DWC align with the concept of preventative care for older women in urban communities. Using semi-structured interviews in selected “DWC communities” located in southern China, this article demonstrates that DWC contributes to addressing older women’s social inclusion by providing preventative care. In addition, we also performed an empirical data analysis that included institutional regulations for DWC design and implementation, publications by DWC communities, and academic research focused on DWC communities. DWC proposes an appealing path for older women to actively engage with and within their community. Furthermore, it offers valuable insights into the potential of a new model of preventative care and our conclusions will serve as a reference for enhancing social involvement among older individuals globally.

Abstract Background Although the chondroprotection of peroxisome proliferator-activated receptor α (PPARα) activation against osteoarthritis (OA) has been revealed, the regulatory mechanism of PPARα deficiency to aggravate osteoarthritic cartilage deterioration remains unclear. Here, we aimed to investigate whether and how autophagy is involved in OA pathological progression. Methods Model of experimental OA was established using destabilization of the medial meniscus in PPARα-KO 129S4/SvJae male mice, followed by histopathological detection of articular cartilage and immunohistochemistry detection of extracellular matrix (ECM) or autophagy-related signal molecules. Meanwhile, human OA chondrocytes obtained from total knee replacement surgery patients with OA were cultured with the pretreatment of IL-1β, followed with the treatment of PPARα agonist WY14643 and the detection of related signal molecules. Results PPARα deficiency aggravated cartilage damage with decreased LC3B level in combination with an increase in P62 level, accompanied with reduced p-Akt and p-ERK levels in PPARα-KO mouse model of experimental OA. On the contrary, PPARα activation by WY14643 promoted ECM synthesis in IL-1β-treated human OA chondrocytes, accompanied with increased LC3B-II/I ratio and Beclin 1 level and decreased P62 and Bcl2 levels. Meanwhile, it was observed that activated ERK and Akt by PPARα activation contributed to the enhancement of autophagy and ECM synthesis in human OA chondrocytes. Conclusions Impaired autophagy contributed to the aggravated deterioration of osteoarthritis articular cartilage by PPARα deficiency associated with the suppression of ERK and Akt, with an implication that triggering PPARα activation ought to be a potential promising therapeutic target for OA therapy.

Abstract Background Medical care avoidance affects individuals’ health status. Previous studies on medical care avoidance have mainly focused on medical costs and people’s satisfaction with medical services. This study investigates whether an individual’s sense of policy alienation toward medical care policy (SPA-M) affects behavioral intention of medical care avoidance, and to what extent an intermediary variable—medical financial risk perception–mediates the relationship between SPA-M and medical care avoidance. Methods A cross-sectional survey was conducted involving 434 people aged 35–59 years from Wuhu, a city in China’s Anhui province. A moderated mediation model was constructed to investigate the research question and sex (biological: male and female) was used as a moderating variable between SPA-M and medical financial risk perception. Results We found that SPA-M significantly impacted medical care avoidance, and that medical financial risk perception played a complete mediating role in this relationship, while sex moderated the relationship between SPA-M and medical financial risk perception. Conclusion This study contributes to the literature by enhancing our understanding of the factors that influence behavioral intention regarding medical care avoidance, deepening our understanding of the role of SPA-M in medical care policy, and expanding the role of sex differences in the analysis of the relationship between SPA-M, medical financial risk perception, and medical care avoidance, offering implications for public and community health.

The composite technology based on friction stir processing (FSP) can enhance the strength of Al alloys while retaining the original toughness and ductility of Al alloys, thus achieving an improvement in the overall performance of the composites. Ni/Al composites were prepared in three typical Al matrixes by optimized FSP, and the effect of in situ generated intermetallic compounds on the strengthening of different Al substrates during the FSP was investigated. It was found that the reinforcing phase of Ni/Al composites was mainly in situ generation of Al3Ni intermetallic compound using energy dispersive spectrometry (EDS) and transmission electron microscopy (TEM), and the more the number and more uniform the distribution of Al3Ni reinforcing phase, the better the mechanical properties of Ni/Al composites. The results indicate that the Ni/Al composites formed from different series of Al alloy matrix, the Ni/6061Al composite has the most remarkable microstructure uniformity, the greatest strength increase and the least elongation decrease, which is conducive to improving its strength without affecting the processing properties of the 6061 Al alloy. The finding opens new opportunities for the preparation of Ni/Al composites with excellent properties from 6061 Al alloys.

Aims: This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower limb amputation (LLA), urinary tract infections (UTI), genital tract infections (GTI), bone fracture, and hypoglycemia in cohort studies.Methods: A systematic search was conducted in the PubMed and Embase databases to identify cohort studies comparing the safety of SGLT-2i versus other glucose-lowering drugs (oGLD) in patients with type 2 diabetes mellitus (T2DM). The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary endpoints were DKA and LLA, while secondary endpoints included UTI, GTI, bone fracture, and hypoglycemia. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated.Results: A total of 9,911,454 patients from 40 cohort studies were included in the analysis. SGLT-2i use was associated with a higher risk of DKA (HR: 1.21, 95% CI: 1.07–1.38, p = 0.003) and GTI (HR: 2.72, 95% CI: 2.48–2.98, p < 0.01). However, it was not associated with an increased risk of LLA (HR: 1.06, 95% CI: 0.92–1.23, p = 0.42), UTI (HR: 0.99, 95% CI: 0.89–1.10, p = 0.83), or bone fracture (HR: 0.99, 95% CI: 0.94–1.04, p = 0.66). Furthermore, SGLT-2i was associated with a reduced risk of hypoglycemia. Furthermore, compared to dipeptidyl peptidase 4 inhibitors, SGLT-2i as a class and individually was associated with an increased risk of DKA. Canagliflozin specifically increased the risk of LLA (HR: 1.19, 95% CI: 1.04–1.36, p = 0.01). The subgroup analysis suggested that SGLT-2i increased the risk of LLA among patients with a history of cardiovascular disease.Conclusion: SGLT-2i versus oGLD was associated with a similar occurrence of LLA, UTI, and bone fracture. However, SGLT-2i was associated with a higher risk of DKA and GTI than oGLD. These findings provide valuable information on the safety profile of SGLT-2i in patients with T2DM and can help inform clinical decision-making.

Objective Failed internal fixation of intertrochanteric fractures (FIF‐ITF) is often treated by conversion hip arthroplasty (CHA). This study aimed to evaluate the results and complications of using standard and long femoral stems in this operation. Methods This retrospective, multi‐center study enrolled 31 total hip arthroplasty (THA) and 23 hemiarthroplasties (HA) cases (30 women, 24 men; mean age 76 years) after FIF‐ITF between 2012 and 2019, divided into two groups: standard stem group (n = 20) and long stem group (n = 34). The initial internal fixation includes 38 cases of proximal femoral nail anti‐rotation (PFNA), eight cases of the dynamic hip screw (DHS), and eight cases of locking proximal femoral plate (LPFP). The indications for CHA included 38 cases of failure of fixation, seven cases of nonunion, and nine cases of avascular necrosis or posttraumatic osteoarthritis. Perioperative data and complications related to fracture and operation were collected, and preoperative and postoperative clinical and radiological data were analyzed. Clinical outcomes were assessed using Harris hip score (HHS) and 36‐item Short Form survey (SF‐36: including physical function (PF) score and body pain (BP) score). Statistical analyses were performed using the chi‐square or Fisher's exact test, and the 2‐sample t‐test or Wilcoxon rank sum test. Results At an average of 5.6 years with a minimum of 2 years follow‐up. A significant overall surgeon‐related complication rate was detected (27.8% [15/54]), five cases had an intraoperative femur fracture, one case had a late periprosthetic femoral fracture, two cases had a stem penetration, one case had a cement leakage, and two patients had an early postoperative dislocation, one infection and three cases of stem loosening or subsidence. Long stems had an increased risk of complication (13/34) compared to standard stems (2/20) (P = 0.031). The operation time and blood loss in the long stem group were higher than those in the standard stem group (P = 0.002; 0.017). HHS and SF‐36 significantly improved in both groups from preoperative to the final follow‐up and did not present significant differences at the final follow‐up (P > 0.05). Conclusion CHA following FIF‐ITF showed a successful mid‐term clinical result, long stem arthroplasty should be approached with caution for the risks of higher complication rate, especially intraoperative femoral fractures.

Understanding the early evolution of coronal mass ejections (CMEs), in particular their initiation, is the key to forecasting solar eruptions and induced disastrous space weather. Although many initiation mechanisms have been proposed, a full understanding of CME initiation, which is identified as a slow rise of CME progenitors in kinematics before impulsive acceleration, remains elusive. Here, with a state-of-the-art thermal magnetohydrodynamics simulation, we determine a complete CME initiation route in which multiple mainstream mechanisms occur in sequence yet are tightly coupled. The slow rise is first triggered and driven by the developing hyperbolic flux tube (HFT) reconnection. Subsequently, the slow rise continues as driven by the coupling of the HFT reconnection and the early development of torus instability. The end of the slow rise, i.e., the onset of the impulsive acceleration, is induced by the start of the fast magnetic reconnection coupled with the torus instability. These results unveil that CME initiation is a complicated process involving multiple physical mechanisms, thus being hardly resolved by a single initiation mechanism.

To understand the magnetic fields of the polar crown filaments (PCFs) at high latitudes near polar regions of the Sun, we perform magnetofrictional numerical simulations on the long-term magnetic evolution of bipolar fields with roughly east–west polarity inversion lines (PILs) in a 3D spherical wedge domain near polar regions. The Coriolis-effect-induced vortical motions at the boundaries of several supergranular cells inject magnetic helicity from the photospheric boundary into the solar atmosphere. Supergranular-scale helicity injection, transfer, and condensation produce strongly sheared magnetic fields. Magnetic reconnections at footpoints of the sheared fields produce magnetic flux ropes (MFRs) with helicity signs consistent with the observed hemispheric helicity rule. The cross-sectional area of MFRs exhibits an uneven distribution, resembling a “foot-node-foot” periodic configuration. Experiments with different tilt directions of PILs indicate that the PCFs preferably form along PILs with the western end close to the polar region. The bending of PILs caused by supergranular flows, forming S-shape (Z-shape) PIL segments, promotes the formation of dextral (sinistral) MFRs. The realistic magnetic models we obtained can serve as starting points for the study of the plasma formation and eruption of PCFs.

Sleep problems in middle-aged and older people can threaten their physical and mental health. Family support is regarded as a key factor that affects sleep quality, but the influence mechanism remains underexplored. This study analyzes the mediating effects of fear of crime (FOC) and loneliness in the relationship between family support and sleep quality, and explores whether gender plays a moderating role between family support and FOC. A questionnaire survey was conducted among 1043 Chinese middle-aged and older people aged 45–93 years. Using 10,000 bootstrapped samples, the study shows that middle-aged and older people who receive more family support have better sleep quality, and FOC and loneliness play mediating role in this association. Gender moderates the relationship between family support and FOC. Compared with men, family support for females has a greater impact on their FOC condition, and the mediating effect of family support on sleep quality through FOC is also greater among women. Family support can affect sleep quality through the chain mediating effect of FOC and loneliness for women. This study provides an in-depth understanding of the relationship between family support and sleep quality.

Bone metastatic cancer-secreted extracellular factors are capable of modifying the bone microenvironment through interacting with bone cells, including osteoblasts. Reticulum ribosome-binding protein 1 (RRBP1) is substantially expressed in certain bone metastatic cancer cells. This study was undertaken to determine whether RRBP1 from bone metastatic cancer cells affects the osteoblastic phenotype expression. Breast and prostate cancer cells, MDA-MB-231 and PC3, were cultured, respectively, followed by collecting conditioned mediums (CMs) and identifying the abundance of RRBP1 in CMs using LC-MS/MS. MC3T3-E1 cells were cultured with a mixed medium (including CMs from shRRBP1-transduced two-type cancer cells) with or without endoplasmic reticulum (ER) stress inhibitor 4-PBA, followed by measuring the levels of osteoblastic phenotype expression and biomarkers of ER stress using western blotting, qPCR, and ARS staining, respectively. Similar experiments were performed in shRrbp1-transduced MC3T3-E1 cells cultured with a mixed medium (including CMs from the two-type cancer cells). Bone formation parameters were measured in the tibia of nude mice injected with shRRBP1-transduced two-type cancer cells using micro-CT analysis. These results showed that RRBP1 is the sole shared high-abundance protein in CMs from the two-type cancer cells, involving osteoblast differentiation. CMs from shRRBP1-transduced two-type cells boosted the osteoblastic phenotype expression partially through increasing ER stress. CMs from the two-type cancer cells partially offset the similar alterations induced by shRrbp1 in MC3T3-E1 cells. Injection with shRRBP1-transduced two-type cells ameliorated the bone lesions in nude mice. Therefore, RRBP1 depletion of bone metastatic cancer enhanced the osteoblastic phenotype expression, suggesting a role of RRBP1 in the bone microenvironment.

This article reports on the evolution of breakdance. Given the inclusion of breakdancing in the 2024 Olympic Games in Paris, France, scholars have generated substantial international research related to breakdance teaching in recent years. However, few researchers have focused on the impact of formal formative assessment on breakdance teachers’ teaching and students’ learning. We wish to contribute to the quality of breakdance teaching and learning by identifying the positive impact of recent research on formative assessment on student learning and designing a formal formative assessment task related to breakdance. This article lays out a framework of formal formative assessment tasks and identifies the positive impact of formative assessment on dance education. Although our work is far from perfect, it does provide a general methodological framework for assessing breakdance students’ abilities in formal educational settings.

DLA-88 is a classical major histocompatibility complex (MHC) class I gene in dogs, and allelic DLA-88 molecules have been divided into two categories named “DLA-88*0” and “DLA-88*5.” The defining difference between the two categories concerns an LQW motif in the α2 domain helical region of the DLA-88*5 molecules that includes the insertion of an extra amino acid compared to MHC class I consensus length. We here show that this motif has been exchanged by recombination between different DLA-88 evolutionary lineages. Previously, with pDLA-88*508:01, the structure of a molecule of the DLA-88*5 category was elucidated. The present study is the first to elucidate a structure, using X-ray crystallography, of the DLA-88*0 category, namely DLA-88*001:04 complexed with β2m and a nonamer peptide derived from canine distemper virus (CDV). The LQW motif that distinguishes DLA-88*5 from DLA-88*0 causes a shallower peptide binding groove (PBG) and a leucine exposed at the top of the α2 domain helix expected to affect T cell selection. Peptide ligand amino acid substitution and pMHC-I complex formation and stability analyses revealed that P2 and P3 are the major anchor residue positions for binding to DLA-88*001:04. We speculate that the distribution pattern of the LQW motif among canine classical MHC class I alleles represents a strategy to enhance allogeneic rejection by T cells of transmissible cancers such as canine transmissible venereal tumor (CTVT).

Osteoarthritis (OA) is an age‐related, chronic degenerative disease. With the increasing median age of the population, this disease has become an important public health problem. New, disease‐modifying therapies are needed. A potential novel molecular target is phospholipase Cγ1 (PLCγ1), a critical enzyme with important functions including calcium signaling regulation and cell proliferation. In rat chondrocytes treated with IL‐1β (20 ng·mL−1 for 36 h), inhibition of PLCγ1 with U73122 (2 μm for 12 h) increased levels and expression of the cartilage matrix components Collagen2 and Aggrecan. This beneficial effect of PLCγ1 inhibition was counteracted by increased chondrocyte apoptosis and necroptosis, increased cell death, and increase levels of ROS, all potentially negative for OA. Combined treatment of IL‐1β + U73122‐treated chondrocytes with inhibitors of apoptosis (Z‐VAD, 10 μm) and necroptosis (Nec‐1, 30 μm) enhanced the increases in levels and expression of Collagen2 and Aggrecan, and prevented the increases in cell death and ROS levels. These results suggest that PLCγ1 inhibition may be a viable approach for an OA therapy, if combined with targeted inhibition of chondrocyte apoptosis and necroptosis.

Abstract Background The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages. Results We found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth hormone (GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca 2+ pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components (P

Solar eruptive activities could occur in weak magnetic field environments and over large spatial scales, which are especially relevant to eruptions involving intermediate or quiescent solar filaments. To handle the large scales, we implement and apply a flux rope embedding method using regularized Biot–Savart laws in the spherical coordinate system. Combined with a potential field source surface model and a magneto-frictional method, a nonlinear force-free field comprising a flux rope embedded in a potential field is constructed. Using the combined nonlinear force-free field as the initial condition, we then perform a zero- β data-constrained magnetohydrodynamic (MHD) simulation for an M8.7 flare at 03:38 UT on 2012 January 23. The MHD model reproduces the eruption process, flare ribbon evolution (represented by the quasi-separatrix layer evolution), and kinematics of the flux rope. This approach could potentially model global-scale eruptions from weak field regions.

Abstract Pomacea canaliculata, a freshwater snail from South America, has rapidly established natural populations from south to north subtropical region in China, since its original introductions in the 1980s. Low temperature in winter is a limiting factor in the geographic expansion and successfully establishment for apple snail populations. There have been some studies on population level of low temperature tolerance for P. canaliculata, yet little is quantified about its life‐history traits in responses to cold temperatures. Whether these responses vary with the acclimation location is also unclear. We investigated the survivorship and longevity of P. canaliculata in responses to cold temperatures and examine whether these responses vary with the location and snail size. We hypothesized that survival of the snails depends on their shell height and the level of low temperature, and P. canaliculata population from the mid-subtropical zone may exhibit the highest viability over the cold thermal range. We sampled P. canaliculata populations from five latitude and longitude ranges of subtropical China: Guangzhou population in southernmost (SM‐GZ), three populations of Yingtan (MR‐YT), Ningbo (MR‐NB), Ya'an (MR‐YA) in midrange, and Huanggang population in northernmost (NM‐HG) subtropical zone. For each P. canaliculata population, survival and longevity at six cold acclimation temperature levels (12, 9, 6, 3, 0, and −3°C) were quantified, and the effects of location and shell height were examined. The MR‐YA population from mid-subtropical zone of China exhibited the highest survival rate and prolonged survival time regardless of the temperature acclimation treatments, whereas the SM‐GZ population from southern subtropical was the most sensitive to cold temperatures, particular temperatures below 9°C. No individuals of the SM‐GZ population could survive after stressed for 30 days (3°C), 5 days (0°C) and 2 days (−3°C), respectively. For each experimental P. canaliculata population held at 3, 0, and −3°C, individuals with intermediate shell height of 15.0–25.0 mm had significantly higher survivals. The results highlight a request of a more thorough investigation on acclimation responses in each of the life table demographic parameters for P. canaliculata, and pose the question of whether natural selection or some genetic changes may have facilitated adaptation in invasive locations.

Abstract Background Chilli veinal mottle virus (ChiVMV), which belongs to the genus Potyvirus of the family Potyviridae, mainly infects solanaceous plants and has caused serious economic losses in Asia and Africa. Tobacco plants infected with ChiVMV suffered from punctate necrosis of leaves, leaf deformation, systemic necrosis of leaves and stems, and eventually plant death. However, ChiVMV infection could not usually be identified given the lack of rapid and efficient detection assays in tobacco plants. Therefore, an isolate of tobacco-infecting ChiVMV (ChiVMV-LZ) was obtained, and a novel isothermal amplification and detection technique, reverse transcription-recombinase polymerase amplification (RT-RPA), was established to detect ChiVMV in tobacco plants. Methods In this study, the full-length genome of ChiVMV-LZ was obtained using reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) assays. The genome sequence of ChiVMV-LZ was characterized by sequence alignment and phylogenetic analysis. Then, a RT-RPA assay was established for rapid and sensitive detection of ChiVMV-LZ in tobacco. Additionally, the established RT-RPA assay was compared to the RT-PCR assay in aspect of sensitivity and application in field-collected tobacco samples. Results ChiVMV-LZ was isolated from diseased tobacco in Luzhou, Sichuan, China. The tobacco plants inoculated with ChiVMV-LZ showed typical symptoms of yellow and round spots on the leaves, and curled and folded leaf margin, similar to those observed on naturally ChiVMV-infected tobacco in the field. The full-length genomic sequence of ChiVMV-LZ was determined to be 9742 nucleotides. Sequence alignment and phylogenetic analysis showed that ChiVMV-LZ was most closely related to ChiVMV-Yp8 isolated from pepper plants in Sichuan province while distantly related to ChiVMV-YN from tobacco in Yunnan province, indicating a possibly geographical differentiation of ChiVMV isolates. Additionally, a RT-RPA assay was established for rapid detection of ChiVMV in tobacco. The RT-RPA has no cross-reaction with other related tobacco viruses and is about 10-fold more sensitive than conventional RT-PCR method. Conclusion The characterization of ChiVMV-LZ infecting tobacco was determined, and the established RT-RPA assay provides a reliable and effective method for rapid detection of ChiVMV in tobacco.

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. Methods GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein–protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan–Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Results In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. Conclusion CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

In order to construct a finite element model of defected articular cartilage, the mechanical behavior and degeneration of articular cartilage after injury were studied. The simplified analytical models of normal and defected articular cartilage and finite element models were established, respectively. Firstly, the analytical solution model and finite element model of hollow defect were constructed by using the elasticity theory of multi-hollow medium. Then, the analytical results of each model were calculated and programmed. The software MATLAB was used for programming calculation. Finally, a finite element solid model of defected articular cartilage was established by using human femoral joint. The solid model was analyzed and calculated by magnetic resonance imaging (MRI). The results showed that when the radius of articular cartilage defect r = 0, i.e. there was no defect in articular cartilage, the internal pore pressure of the defect cartilage was the largest, and its pore pressure value was 27×103pa. When the depth of articular cartilage defect r = 0, i.e. there was no defect in articular cartilage, the internal pore pressure of the defect cartilage was the largest, and its pore pressure value was 27.5×103pa, and it gradually decreased towards the outer boundary of cartilage. When the surface of femoral cartilage began to defect, with the increase of the depth of the defect (from shallow to deep), the maximum pore pressure in the defect cartilage gradually decreased, but the speed is slowly. With the increase of the defect radius, that is, the area of the defect, the maximum pore pressure in the defect cartilage gradually decreased. When there was no defect of articular cartilage, the internal pore pressure of the defect cartilage was the maximum, the value of pore pressure was 8.7×103pa, the value of pore pressure at the contact position of femoral cartilage was the largest, and it gradually decreased towards the outer boundary of cartilage. At the same location, the pore pressure of normal cartilage was significantly higher than that of defected cartilage. With the change of defect location, the pore pressure was reduced accordingly. Moreover, when the defect position moved from the outside to the inside, the corresponding pore pressure value was decreased gradually. To sum up, the finite element model of defected articular cartilage based on porous elasticity theory has better calculation ability, which proves the validity of the finite element software, and provides a strong basis for future model establishment and clinical treatment of articular cartilage. Keywords: Articular cartilage, Finite element simulation, Fluid flow, MRI, Permeability

Purpose: This study explored the association between peripheral blood oxytocin (OT) and social anxiety disorder (SAD) and cue-induced cravings in female heroin addicts. The effect of exercise on alleviation of SAD and OT levels was also explored.Methods: A total of 72 females with heroin dependence were assigned to three groups based on SAD severity. The three groups were Non-SAD control, SAD control, and SAD exercise groups. Subjects in the SAD exercise group underwent aerobic exercise and resistance training for 8 weeks (60 min/day, 5 days/week). Enzyme-linked immunosorbent assay analysis and Liebowitz Social Anxiety Scale (LSAS) scores were used to determine plasma OT concentration and SAD, respectively. Cue-induced craving was assessed using Visual Analog Scale (VAS) and Desires for Drug Questionnaire (DDQ). Mixed-effect analysis of variance and Pearson correlation analysis were used to explore the effect and correlation between different parameters.Results: OT levels in the SAD exercise group were significantly high after exercise (p < 0.01). LSAS, VAS, and DDQ (“Desire and Intention” and “Negative reinforcement”) scores in the SAD exercise group were significantly lower after exercise (p < 0.01). Plasma OT level was negatively correlated with LSAS score (r = −0.534, p < 0.001), VAS score (r = −0.609, p < 0.001), “Desire and Intention” score (r = −0.555, p < 0.001), and “Negative reinforcement” score (r = −0.332, p < 0.01) and positively correlated with the “control” score (r = 0.258, p < 0.05). LSAS was positively correlated with VAS score (r = 0.588, p < 0.001) and “Desire and Intention” score (r = 0.282, p < 0.05).Conclusions: The findings of the present study indicate that plasma OT is a potential peripheral biomarker for prediction of the severity of social anxiety in female heroin withdrawal patients. Aerobic exercise combined with resistance training plus incremental load for 8 weeks can increase plasma OT levels and significantly reduce severity of SAD and cue-induced cravings in female heroin addicts.

Elderly patients with non-small-cell lung cancer (NSCLC) exhibit worse reactions to anticancer treatments. Adenocarcinoma (AC) is the predominant histologic subtype of NSCLC, is diverse and heterogeneous, and shows different outcomes and responses to treatment. The aim of this study was to establish a nomogram that includes the important prognostic factors based on the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. We collected 53,694 patients of older than 60 who have been diagnosed with lung AC from the SEER database. Univariate and multivariate Cox regression analyses were used to screen the independent prognostic factors, which were used to construct a nomogram for predicting survival rates in elderly AC patients. The nomogram was evaluated using the concordance index (C-index), calibration curves, net reclassification index (NRI), integrated discrimination improvement (IDI), and decision-curve analysis (DCA). Elderly AC patients were randomly divided into a training cohort and validation cohort. The nomogram model included the following 11 prognostic factors: age, sex, race, marital status, tumor site, histologic grade, American Joint Committee for Cancer (AJCC) stage, surgery status, radiotherapy status, chemotherapy status, and insurance type. The C-indexes of the training and validation cohorts for cancer-specific survival (CSS) (0.832 and 0.832, respectively) based on the nomogram model were higher than those of the AJCC model (0.777 and 0.774, respectively). The CSS discrimination performance as indicated by the AUC was better in the nomogram model than the AJCC model at 1, 3, and 5 years in both the training cohort (0.888 vs. 0.833, 0.887 vs. 0.837, and 0.876 vs. 0.830, respectively) and the validation cohort (0.890 vs. 0.832, 0.883 vs. 0.834, and 0.880 vs. 0.831, respectively). The predicted CSS probabilities showed optimal agreement with the actual observations in nomogram calibration plots. The NRI, IDI, and DCA for the 1-, 3-, and 5-year follow-up examinations verified the clinical usability and practical decision-making effects of the new model. We have developed a reliable nomogram for determining the prognosis of elderly AC patients, which demonstrated excellent discrimination and clinical usability and more accurate prognosis predictions. The nomogram may improve clinical decision-making and prognosis predictions for elderly AC patients.

Structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar. However, whereas pMHC-II complexes include similar-sized IIα and IIβ chains, pMHC-I complexes include a heavy chain (HC) and a single domain molecule β2-microglobulin (β2-m). Recently, we elucidated several pMHC-I and pMHC-II structures of primitive vertebrate species. In the present study, a comprehensive comparison of pMHC-I and pMHC-II structures helps to understand pMHC structural evolution and supports the earlier proposed—though debated—direction of MHC evolution from class II-type to class I. Extant pMHC-II structures share major functional characteristics with a deduced MHC-II-type homodimer ancestor. Evolutionary establishment of pMHC-I presumably involved important new functions such as (i) increased peptide selectivity by binding the peptides in a closed groove (ii), structural amplification of peptide ligand sequence differences by binding in a non-relaxed fashion, and (iii) increased peptide selectivity by syngeneic heterotrimer complex formation between peptide, HC, and β2-m. These new functions were associated with structures that since their establishment in early pMHC-I have been very well conserved, including a shifted and reorganized P1 pocket (aka A pocket), and insertion of a β2-m hydrophobic knob into the peptide binding domain β-sheet floor. A comparison between divergent species indicates better sequence conservation of peptide binding domains among MHC-I than among MHC-II, agreeing with more demanding interactions within pMHC-I complexes. In lungfishes, genes encoding fusions of all MHC-IIα and MHC-IIβ extracellular domains were identified, and although these lungfish genes presumably derived from classical MHC-II, they provide an alternative mechanistic hypothesis for how evolution from class II-type to class I may have occurred.

Abstract Background Autophagy induction is an effective approach for OA therapy. IL-1β is one of the major inflammatory cytokines linked to OA pathological progression, and its receptor blockade interrupts OA cartilage destruction. The objective of this study was to decipher the link between autophagy and regulatory mechanism of IL-1β and to investigate the effect of IL-1β receptor blockade by IL-1 receptor antagonist (IL-1Ra) combined with or without an autophagy inducer (TAT-Beclin1) on extracellular matrix (ECM) in OA chondrocytes in vitro and in vivo. Methods IL-1β-treated rat and human OA chondrocytes were cultured in response to IL-1Ra. The expression and distribution of signal molecules regulating ECM synthesis and autophagy were investigated via western blotting, immunoprecipitation, real-time PCR, immunofluorescence, and transmission electron microscope technique. Furthermore, after intra-articular injection of IL-1Ra, TAT-Beclin1, and a combination of both in a rat OA model established by anterior cruciate ligament transection and medial meniscus resection, the morphological changes of cartilage and related signal molecule expression levels were monitored using H.E., Safranin O-Fast green, and immunohistochemistry staining. Results Reduced autophagy by IL-1β contributed to ECM degradation, and blockade of IL-1β by IL-1Ra restored autophagy and attenuated ECM degradation in rat and human OA chondrocytes, as well as in a rat OA model. Akt/mTOR/ULK1, Akt/mTOR/NF-κB, and LC3B deacetylation were involved in autophagy regulated by IL-1β. Intra-articular injection of IL-1Ra combined with TAT-Beclin1 was more effective than IL-1Ra alone. Conclusions IL-1Ra restored autophagy and attenuated ECM degradation, with an implication that blocking IL-1β combined with enhancing autophagy might be a potential therapeutic strategy for OA.

The micropolymorphism of major histocompatibility complex class I (MHC-I) can greatly alter the plasticity of peptide presentation, but elucidating the underlying mechanism remains a challenge. Here we investigated the impact of the micropolymorphism on peptide presentation of swine MHC-I (termed swine leukocyte antigen class I, SLA-I) molecules via immunopeptidomes that were determined by our newly developed random peptide library combined with the mass spectrometry (MS) de novo sequencing method (termed RPLD–MS) and the corresponding crystal structures. The immunopeptidomes of SLA-1*04:01, SLA-1*13:01, and their mutants showed that mutations of residues 156 and 99 could expand and narrow the ranges of peptides presented by SLA-I molecules, respectively. R156A mutation of SLA-1*04:01 altered the charge properties and enlarged the volume size of pocket D, which eliminated the harsh restriction to accommodate the third (P3) anchor residue of the peptide and expanded the peptide binding scope. Compared with 99Tyr of SLA-1*0401, 99Phe of SLA-1*13:01 could not form a conservative hydrogen bond with the backbone of the P3 residues, leading to fewer changes in the pocket properties but a significant decrease in quantitative of immunopeptidomes. This absent force could be compensated by the salt bridge formed by P1-E and 170Arg. These data illustrate two distinguishing manners that show how micropolymorphism alters the peptide-binding plasticity of SLA-I alleles, verifying the sensitivity and accuracy of the RPLD-MS method for determining the peptide binding characteristics of MHC-I in vitro and helping to more accurately predict and identify MHC-I restricted epitopes.

Summary: In this work, chicken HPAIV H5N1 epitope-specific TCRαβ (ch-TCRαβ) was isolated and its structure was determined. The Cα domain of ch-TCRαβ does not exhibit the typical structure of human TCRαβ, and the DE loop extends outward, resulting in close proximity between the Cα domain of ch-TCRαβ and CD3εδ/γ. The FG loop of the Cβ domain of ch-TCRαβ is shorter. The changes in the C domains of ch-TCRαβ and the difference in chicken CD3εδ/γ confirm that the complexes formed by TCRαβ and CD3εδ/γ differ from those in humans. In the chicken complex, a positively charged cleft is formed between the two CDR3 loops that might accommodate the acidic side chains of the chicken pMHC-I-bound HPAIV epitope intermediate portion oriented toward ch-TCRαβ. This is the first reported structure of chicken TCRαβ, and it provides a structural model of the ancestral TCR system in the immune synapses between T cells and antigen-presenting cells in lower vertebrates.

The CD8αα homodimer is crucial to both thymic T cell selection and the antigen recognition of cytotoxic T cells. The CD8-pMHC-I interaction can enhance CTL immunity via stabilizing the TCR-pMHC-I interaction and optimizing the cross-reactivity and Ag sensitivity of CD8+ T cells at various stages of development. To date, only human and mouse CD8-pMHC-I complexes have been determined. Here, we resolved the pBF2*1501 complex and the cCD8αα/pBF2*1501 and cCD8αα/pBF2*0401 complexes in nonmammals for the first time. Remarkably, cCD8αα/pBF2*1501 and the cCD8αα/pBF2*0401 complex both exhibited two binding modes, including an “antibody-like” mode similar to that of the known mammal CD8/pMHC-I complexes and a “face-to-face” mode that has been observed only in chickens to date. Compared to the “antibody-like” mode, the “face-to-face” binding mode changes the binding orientation of the cCD8αα homodimer to pMHC-I, which might facilitate abundant γδT cells to bind diverse peptides presented by limited BF2 alleles in chicken. Moreover, the forces involving in the interaction of cCD8αα/pBF2*1501 and the cCD8αα/pBF2*0401 are different in this two binding model, which might change the strength of the CD8-pMHC-I interaction, amplifying T cell cross-reactivity in chickens. The coreceptor CD8αα of TCR has evolved two peptide-MHC-I binding patterns in chickens, which might enhance the T cell response to major or emerging pathogens, including chicken-derived pathogens that are relevant to human health, such as high-pathogenicity influenza viruses.

Energy service companies (ESCOs) play crucial role in building energy efficiency retrofit sector. However limited access to green financing has prevented ESCOs in their expansions in China. This paper, based on a survey of 469 samples and on-site visiting to and interviewing relevant 50 actors of ESCOs, financial institutions and local housing authorities, identifies main barriers of accessing to green financing at both systemic policy level and operational meso and micro level in China, and analyzes good practices at local level that overcome the barriers. The paper concludes that, although there are barriers existing at the policy level in China, substantial attentions and priorities should be given to take actions for overcoming the barriers existed at the operational meso and micro level. The paper suggests that the good practices of capacity building for ESCOs and local financial sector, intensifying participation of intermediate organizations or facilitators and diversifying financial sources and funding mechanisms and models that emerge from the local level should be disseminated in China.

Summary: Contemporary antigen presentation knowledge is based on the existence of a single β2m locus, and a classical MHC class I forms a complex with a peptide (i.e., pMHC-I) to trigger CTL immunity. However, two β2m loci have been found in diploid bony fish; the function of the two β2m molecules is unclear. Here, we determined the variant peptide profiles originating from different products of the β2m loci binding to the same MHC-I molecule and further solved the crystal structures of the two pMHC-I molecules (i.e., pCtid-UAA-β2m-2 and pCtid-UAA-β2m-1-II). Of note, in pCtid-UAA-β2m-2, a unique hydrogen bond network formed in the bottom of the peptide-binding groove (PBG) led to α2-helix drift, ultimately leading to structural changes in the PBG. The mechanism of the change in peptide presentation profiles by β2m molecules is illustrated. The results are also of great significance for antivirus and antitumor functions in cold-blooded vertebrates and even humans.

This paper studied the fumigating activity of Litsea cubeba oil and citral on Solenopsis invicta, identified and analyzed the chemical constituents and volatile components of L. cubeba oil via solid-phase microextraction which were then identified via gas chromatography-mass spectrometry. The results showed that citral and (z)-3,7-dimethylocta-2,6-diena were the main components of L. cubeba oil, as well as its volatile compounds. According to the experimental results, L. cubeba oil and citral had good fumigating activity on workers, and also had significant inhibition on the walking ability and climbing ability of workers. At the same time, the effects of the two agentia on the fumigating activity and behavioral inhibition of microergate were stronger than those of macroergate. After treating with L. cubeba oil and citral for 24 hours, the walking rate and grasping rate of microergate were both 0 %. The results showed that L. cubeba oil and citral had good control effect on S. invicta.

Purpose: The aim of this study was to evaluate the potential neurotrophic factors and expression of neurotrophin receptors in peripheral blood mononuclear cells linked with the antidepressant action of exercise intervention during protracted methamphetamine (METH) abstinence.Materials and Methods: A total of 72 male METH addicts, including 47 individuals with depression and 25 individuals without depression, were recruited in this study. Individuals with depression were divided into the depression control group and the depression exercised group. Consequently, 12 weeks of supervised exercise intervention was applied. Depression and anxiety were analyzed; plasma brain-derived neurotrophic factor (BDNF), neuronal growth factor (NGF), neurotrophin-3 (NT-3), NT-4, and proBDNF levels were tested using enzyme-linked immunosorbent assay; the mRNA expressions of TrkA, TrkB-FL, TrkB-T1, TrkCB, and P75NTR in peripheral blood mononuclear cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR).Results: NT-4 plasma levels were correlated with depression (r = −0.330, p = 0.005), which remained significant after Bonferroni correction. In addition, the BDNF and NT-3 levels in the plasma were significantly correlated with depression (r = −0.268, p = 0.023; r = −0.259, p = 0.028), but did not reach significance after Bonferroni correction. The BDNF, NT-3, and NT-4 plasma levels were significantly different between the depressive control group and the depressive exercise group using pre-exercise values as the covariate. The fold changes in TrkB-FL and TrkB-T1 mRNA in peripheral blood mononuclear cells between the post-exercise and pre-exercise demonstrated a remarkable decrease (fold change = −11.056 and −39.055).Conclusions: Exercise intervention can alleviate depression and anxiety during protracted METH abstinence. Decrease in BDNF and the expression of TrkB in peripheral blood mononuclear cells occur following the exercise intervention.

To investigate CTL epitope applications in swine, SLA-1*1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1*1502 (pSLA-1*1502) complexes, and the crystal structure of the SLA-1*1502 complex with one peptide (NSP9-TMP9) was determined. The NSP9-TMP9 peptide conformation presented by pSLA-1*1502 is different from that of the peptides presented by the known pSLA-1*0401 and pSLA-3*hs0202 complexes. Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper. The D pocket of pSLA-1*1502 is unique and is important for peptide binding. Next, the potential SLA-1*1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1*1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. The tetrameric complex of SLA-1*1502 and NSP9-TMP9 was constructed and examined. Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated. The SPF swine expressing the SLA-1*1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group. NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-γ expression. Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine.

To provide a vehicle for sustained release of cartilage-protective agent for the potential application of osteoarthritis (OA) treatment, we developed a kartogenin (KGN)-incorporated thermogel for intra-articular injection. We fabricated a poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) thermogel as a KGN carrier for IA injection. OA chondrocytes were cultured in thermogel with or with no KGN to investigate the effect of KGN thermogel on cartilage matrix. The in vivo effect of KGN thermogel on OA was examined in a rabbit OA model. The KGN thermogel showed a sustained in vitro release of KGN for 3 weeks. OA chondrocytes proliferated well both in thermogel and KGN thermogel. In addition, OA chondrocytes produced higher amount of [type 2 collagen (COL-2) and glycosaminoglycan (GAG)], as well as lower level of matrix metalloproteinase 13 (MMP-13) in KGN thermogel that those in thermogel with no addition of KGN. The gene analysis supported that KGN thermogel enhanced expression of hyaline-cartilage specific genes Col 2 and AGC, and inhibited the expression of MMP-13. Compared with intra-articular injection of saline or thermogel containing no KGN, KGN thermogel can enhance cartilage regeneration and inhibit joint inflammation of arthritic knees in a rabbit ACLT-induced OA model at 3 weeks after the injection. Therefore, the KGN-incorporated PLGA–PEG–PLGA thermogel may provide a novel treatment modality for OA treatment with IA injection.

Hypertension is the most important risk factor for cardiovascular diseases worldwide. However, the underlying molecular mechanisms of hypertension are complex and remain largely elusive. Here, we described a novel, microRNA-dependent therapeutic strategy for hypertension. First, we found that plasma microRNA-21-3p (miR-21-3p) levels were significantly reduced both in hypertensive patients and spontaneously hypertensive rats (SHRs) when compared with normal controls. In a series of experiments to dissect the role of miR-21-3p in hypertension, we showed that intravenous delivery of recombinant adeno-associated virus (rAAV)-mediated miR-21-3p expression induced a persistent attenuation of hypertension, with marked amelioration of target organ damages, including cardiac hypertrophy and fibrosis and artery and kidney fibrosis in SHRs, whereas miR-21-3p tough decoys (TuDs) counteracted the above effects. Computational prediction coupled with biochemical experiments revealed that the miR-21-3p-mediated hypotensive reduction effect was accomplished by regulating phenotypic switch of vascular smooth muscle cells (VSMCs) via suppression of the adrenal α2B-adrenergic receptor (ADRA2B) in arteries. Furthermore, we observed that activation of transcription factor NF-κB and SRF significantly increased the expression of miR-21-3p in VSMCs. In summary, our study is the first to identify a novel role and mechanism of miR-21-3p in blood pressure control and provides a possible strategy for hypertension therapy using rAAV-miR-21-3p.

Analysis of observational data to pinpoint impact of land cover change on local rainfall is difficult due to multiple environmental factors that cannot be strictly controlled. In this study we use a statistical approach to identify the relationship between removal of tree cover and rainfall with data from best available sources for two large areas in Australia. Gridded rainfall data between 1979 and 2015 was used for the areas, while large scale (exogenous) effects were represented by mean rainfall across a much larger area and climatic indicators, such as Southern Oscillation Index and Indian Ocean Dipole. Both generalised additive modelling and step trend tests were used for the analysis. For a region in south central Queensland, the reported change in tree clearing between 2002–2005 did not result in strong statistically significant precipitation changes. On the other hand, results from a bushfire affected region on the border of New South Wales and Victoria suggest significant changes in the rainfall due to changes in tree cover. This indicates the method works better when an abrupt change in the data can be clearly identified. The results from the step trend test also mainly identified a positive relationship between the tree cover and the rainfall at p

The expansion of photovoltaics in German cities has so far fallen short of expectations. The concept of ‘tenant electricity’ (‘Mieterstrom’ in German), in which tenants of a building are supplied with solar power produced on site, offers great potential here. A study on behalf of the German Federal Ministry for Economic Affairs and Energy estimated the number of tenant households with good conditions for solar tenant electricity at 3.8 million. At the same time, the federal tenant electricity promotion scheme has been in place since 2017, but only about 1% of the annual budget has been claimed. The aim of this study is to identify the barriers for and drivers of diffusion of the tenant electricity model. To this end, a qualitative document analysis and a range of semi-structured expert interviews have been conducted. The theoretical framework used to guide the analysis is the multi-level perspective. The main barrier found for tenant electricity diffusion is the legal framework on the regime level, which also leads to high transaction costs of implementing tenant electricity. A social barrier is the inertia of some residents to actively concern themselves with their electricity supply and switch to a tenant electricity contract. Among its drivers are long-term trends such as the increasing electricity demand in urban areas, technical developments like blockchain technology and the increasing deployment of smart meters, and the EU Renewable Energy Directive. As long as the restrictive legal framework prevails, the further diffusion of tenant electricity will remain limited.

Phosphoinositide specific phospholipase Cγ (PLCγ) activates diacylglycerol (DAG)/protein kinase C (PKC) and inositol 1,4,5-trisphosphate (IP3)/Ca2+/calmodulin-dependent protein kinase II (CaMK II) axes to regulate import events in some cancer cells, including gastric adenocarcinoma cells. However, whether DAG/PKCδ and IP3/Ca2+/CaMK IIβ axes are simultaneously involved in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells and the underlying mechanism are not elucidated. Here, we investigated the role of DAG/PKCδ or CaMK IIβ in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells, using the BGC-823 cell line. The results indicated that the inhibition of PKCδ and CaMK IIβ could block cell proliferation and migration of BGC-823 cells as well as the effect of inhibiting PLCγ1, including the decrease of cell viability, the increase of apoptotic index, the down-regulation of matrix metalloproteinase (MMP) 9 expression level, and the decrease of cell migration rate. Both DAG/PKCδ and CaMK IIβ triggered protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/S6 pathway to regulate protein synthesis. The data indicate that DAG/PKCδ and IP3/Ca2+/CaMK IIβ operate in parallel to each other in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells through Akt/mTOR/S6 pathway, with important implication for validating PLCγ1 as a molecular biomarker in early gastric cancer diagnosis and disease surveillance.

China’s regular energy statistics does not include the building sector, and data on building energy demand is included in other types of energy consumption in the Energy Balance Sheet (EBS). Therefore data on building energy demand is not collected based on statistics, but rather calculated or estimated by various approaches in China. This study aims at developing and testing China’s building energy statistics by applying an adapted EBS. The advantage of the adapted EBS is that statistical data is from the regular statistical system and no additional statistical efforts are needed. The research result shows that the adapted EBS can be included in China regular energy statistical system and can be standardized in a transparent way. Testing of the adapted EBS shows that China’s building energy demand has shown an annual increase of 7.6% since 2001, and a lower contribution to the total energy demand as compared to the developed world. There is also a close link to lifestyle and living standard while industrial energy demand is mainly driven by economy and decoupling of building energy demand with increasing of building floor area, this is due to a considerable improvement of building energy efficiency. The adapted EBS creates a method for China conducting statistics of building energy consumption at the sector level in a uniform way and serves as the basis for any sound building energy efficiency policy decisions.

The issue of whether ERK activation determines matrix synthesis or degradation in osteoarthritis (OA) pathogenesis currently remains controversial. Our previous study shows that PLCγ1 and mTOR are involved in the matrix metabolism of OA cartilage. Investigating the interplays of PLCγ1, mTOR and ERK in matrix degradation of OA will facilitate future attempts to manipulate ERK in OA prevention and therapy. Here, cultured human normal chondrocytes and OA chondrocytes were treated with different inhibitors or transfected with expression vectors, respectively. The levels of ERK, p-ERK, PLCγ1, p-PLCγ1, mTOR, p-mTOR and MMP-13 were then evaluated by Western blotting analysis. The results manifested that the expression level of ERK in human OA chondrocytes was lower than that in human normal articular chondrocytes, and the up-regulation of ERK could promote matrix synthesis, including the decrease in MMP-13 level and the increase in Aggrecan level in human OA chondrocytes. Furthermore, the PLCγ1/ERK axis and a mutual inhibition of mTOR and ERK were observed in human OA chondrocytes. Interestingly, activated ERK had no inhibitory effect on MMP-13 expression in PLCγ1-transformed OA chondrocytes. Combined with our previous study, the non-effective state of ERK activation by PLCγ1 on MMP-13 may be partly attributed to the inhibition of the PLCγ1/mTOR axis on the PLCγ1/ERK axis. Therefore, the study indicates that the mutual inhibition of ERK and mTOR is involved in PLCγ1-mediated MMP-13 expression in human OA chondrocytes, with important implication for the understanding of OA pathogenesis as well as for its prevention and therapy.

Urbanization and climate change are amongst the greatest challenges of the 21st century. In the “Low Carbon Future Cities” project (LCFC), three important problem dimensions are analysed: current and future GHG emissions and their mitigation (up to 2050); resource use and material flows; and vulnerability to climate change. The industrial city of Wuxi has been the Chinese pilot city of the project. To establish the pathway for a low carbon future, it is crucial to understand the current situation and possible future developments. The paper presents the key results of the status quo analysis and the future scenario analysis carried out for Wuxi. Two scenarios are outlined. The Current Policy Scenario (CPS) shows the current most likely development in the area of energy demand and GHG emissions until 2050. Whereas the extra low carbon scenario (ELCS) assumes a significantly more ambitious implementation, it combines a market introduction of best available technologies with substantial behavioural change. All scenarios are composed of sub-scenarios for the selected key sectors. Looking at the per capita emissions in Wuxi, the current levels are already high at around 12 tonnes CO2 per capita compared to Western European cities. Although Wuxi has developed a low carbon plan, the projected results under current policies (CPS) show that the total emissions would increase to 23.6 tonnes CO2 per capita by 2050. If the ELCS pathway was to be adopted, these CO2 emission levels could be reduced to 6.4 tonnes per capita by 2050. However, this is not a problem unique to Wuxi or China. A comprehensive rethink at global level on how to increase energy and resource efficiency and sustainability is required.