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Abstract The long‐term durability of triboelectric nanogenerators (TENGs) remains a main challenge for practical applications because of inevitable material abrasion and wear, especially for sliding TENGs. Herein, an inorganic triboelectric pair composed of diamond‐like carbon (DLC) and glass with excellent durability and triboelectric output for sliding‐mode TENGs is proposed. This triboelectric pair possesses a low coefficient of friction and little abrasion and accordingly excellent durability (>500 000 cycles). Moreover, compared with the traditional copper‐polytetrafluoroethylene (Cu‐PTFE) TENG with maximum transferred charges of 50 nC, those of the DLC‐glass TENG reaches 141 nC. Due to the low‐friction and high hardness of the triboelectric pair, the output quickly recovers after simply cleaning wear debris. The DLC‐glass TENG demonstrates an output power density of 530 mW m−2 and a fourfold faster capacitor charging speed than the Cu‐PTFE TENG. Compared to the reported durable TENGs via structure optimization and interface lubrication, the DLC‐glass TENG shows higher outputs and simpler structure. This DLC‐glass pair structure is also introduced into a spherical TENG for blue energy harvesting with excellent durability. The inorganic triboelectric pair with excellent mechanical durability and electrical performance proposed in this work shows huge prospects for practical applications of TENGs.

Abstract Given recent global endeavors to increase protected area coverage, it is crucial to comprehensively evaluate the efficacy of various area‐based conservation strategies in effectively reducing biodiversity loss. Here, we investigated the responses of wildlife populations to different protection levels and environmental variables at the landscape scale in the Katavi–Rukwa Ecosystem, western Tanzania. To this end, we conducted line distance sampling surveys and counted the dung of six target mammal species (elephant, giraffe, buffalo, zebra, topi, and hartebeest) along foot transects within areas differing in protection levels (from strict to less‐strictly protected: national park, game reserve, forest reserve, game‐controlled area, and unprotected areas). Based on these dung counts, we modeled the spatial distribution of these six mammal species using a species‐specific density surface modeling framework. We found consistent effects of protection level and land use variables on the spatial distribution of the target mammal species: dung densities were highest in the national park and game reserves, intermediate in less‐strictly protected areas, and lowest in unprotected areas. Beyond species‐specific environmental predictors for dung densities, our results highlight consistent negative associations between dung densities of the target species and distance to cropland and avoidance of areas in proximity to houses. Our findings underpin differences in ecological effectiveness of protected areas within one ecosystem. Protection level and land use play crucial roles in moderating the spatial distribution of all considered mammal species. Our findings suggest that a landscape approach needs to guide effective conservation across the entire protection gradient of the Katavi–Rukwa Ecosystem.

Early data suggested that CC‐115, a clinical molecule, already known to inhibit the mammalian target of rapamycin kinase (TORK) and DNA‐dependent protein kinase (DNA‐PK) may have additional targets beyond TORK and DNA‐PK. Therefore, we aimed to identify such target(s) and investigate a potential therapeutic applicability. Functional profiling of 141 cancer cell lines revealed inhibition of kinase suppressor of morphogenesis in genitalia 1 (SMG1), a key regulator of the RNA degradation mechanism nonsense‐mediated mRNA decay (NMD), as an additional target of CC‐115. CC‐115 treatment showed a dose‐dependent increase of SMG1‐mediated NMD transcripts. A subset of cell lines, including multiple myeloma (MM) cell lines sensitive to the endoplasmic reticulum stress‐inducing compound thapsigargin, were highly susceptible to SMG1 inhibition. CC‐115 caused the induction of UPR transcripts and cell death by mitochondrial apoptosis, requiring the presence of BAX/BAK and caspase activity. Superior antitumor activity of CC‐115 over TORK inhibitors in primary human MM cells and three xenograft mouse models appeared to be via inhibition of SMG1. Our data support further development of SMG1 inhibitors as possible therapeutics in MM.

Chronic lymphocytic leukemia (CLL) cells are highly dependent on microenvironmental cells and signals. The lymph node (LN) is the critical site of in vivo CLL proliferation and development of resistance to both chemotherapy and targeted agents. We present a new model that incorporates key aspects of the CLL LN, which enables investigation of CLL cells in the context of a protective niche. We describe a three-dimensional (3D) in vitro culture system using ultra-low attachment plates to create spheroids of CLL cells derived from peripheral blood. Starting from CLL:T cell ratios as observed in LN samples, CLL activation was induced by either direct stimulation and/or indirectly via T cells. Compared with two-dimensional cultures, 3D cultures promoted CLL proliferation in a T cell-dependent manner, and enabled expansion for up to 7 weeks, including the formation of follicle-like structures after several weeks of culture. This model enables high-throughput drug screening, of which we describe response to Btk inhibition, venetoclax resistance, and T cell-mediated cytotoxicity as examples. In summary, we present the first LN-mimicking in vitro 3D culture for primary CLL, which enables readouts such as real-time drug screens, kinetic growth assays, and spatial localization. This is the first in vitro CLL system that allows testing of response and resistance to venetoclax and Bruton's tyrosine kinase inhibitors in the context of the tumor microenvironment, thereby opening up new possibilities for clinically useful applications.

Abstract Protected and conserved areas (PCAs) target at biodiversity conservation and human well‐being, but often reflect low levels of effectiveness. Understanding PCAs social‐ecological systems in which people and nature interact in so‐called social‐ecological interactions is key to understanding the roots of (in)effectiveness, and to leverage change toward resilient and sustainable systems. Despite this potential, social‐ecological interactions in PCAs are commonly neglected in effectiveness evaluations. To address this gap, we elaborated a thorough understanding of the social‐ecological interactions in PCAs through the following steps: In a first step, we extracted from scientific literature which social‐ecological interactions influence the effectiveness of PCAs in general and derived influencing factors which shape those interactions. Based on these insights, we developed an analytical framework, which, in a second step, we applied to a case study in North Luangwa, Zambia. We elucidated three dimensions of social‐ecological interactions occurring in the study area: care (e.g., conservation programs), conflict (e.g., disease transmission), and use (e.g., hunting). We visualized relationships between these interactions and associated key variables in a causal loop diagram. Finally, we drew on the case study in Zambia's Luangwa Valley to propose system‐specific metrics for key variables central to the social‐ecological structure of the study area to make effectiveness measurable. Our approach allows for linking site‐specific social‐ecological interactions to PCA effectiveness. More generally, our findings call for the consideration of the relationships between people and nature when assessing conservation effectiveness.

Abstract Background Polycystic ovary syndrome (PCOS) affects 5%–10% of women in their reproductive years. Most women with PCOS struggle with obesity during their entire life. Knowing which determinants contribute to a successful lifestyle change is important to optimize treatment options for women with PCOS. Objective This analysis of secondary outcome measures aimed to determine factors of ≥5% weight loss and dropout in all arms of the study and separately in the lifestyle intervention (LI) and control (care as usual [CAU]) groups. Study design Women diagnosed with PCOS (N = 183) and a Body Mass Index (BMI) above 25 kg/m2 were included. Participants were assigned to (1) 20 lifestyle sessions involving cognitive behavioral therapy (CBT), (2) 20 lifestyle sessions involving CBT with additional short message service (SMS), or (3) to control (CAU). A generalized linear regression was performed to identify determinants of ≥5% weight loss. Logistic regression was performed to identify determinants of dropout. All models were corrected by including baseline weight as a covariate. Results LI (OR 4.906, p = .001) was associated with ≥5% weight loss, while higher depression scores (OR 0.549, p = .013) had a negative association. Restraint eating was a positive factor for ≥5% weight loss in LI but a negative in CAU. Higher baseline weight (OR 1.033, p = .006), LI with SMS (OR 4.424, p = .002), and higher levels of androstenedione (OR 1.167, p = .026) were associated with dropout. Conclusions Depression and eating behavior were associated with ≥5% weight loss. Women with PCOS should be screened for depression and eating behavior before a LI.

Abstract Despite being key conservation instruments, the ecological effectiveness of protected areas (PAs) is contested. To assess the ecological effectiveness of PAs in the Katavi‐Rukwa Ecosystem (KRE) in western Tanzania, we investigated temporal changes in land‐use and population densities of six large mammal target species (elephant, buffalo, giraffe, zebra, topi, and hartebeest) across areas with different conservation category, ranging from unprotected to strictly protected. During six survey periods between 1991 and 2018, we analyzed data from remote sensing and aerial wildlife surveys to derive (i) spatiotemporal patterns of cropland cover in relation to protection category; (ii) population densities of the six‐target species; and (iii) distribution of these species across protection category, land‐use and environmental variables. During the surveyed period, cropland increased from 3.4 % to 9.6 % on unprotected land and from ≤0.05 % to

The ligand of the receptor activator of NF-κB (RANKL) is a key molecule in the formation of osteoclasts, the key cells that cause the disease-associated alveolar bone resorption in periodontitis. We hypothesized that polymorphonuclear leukocytes (PMNs), found as the most prominent cells of inflamed periodontal tissues, could play an important role in providing signals to trigger osteoclastogenesis and thus activating pathological bone resorption in periodontitis. RANKL expression was investigated on circulatory PMNs (cPMNs) and oral PMNs (oPMNs) taken from both controls and periodontitis patients. On average, 2.3% and 2.4% RANKL expression was detected on the cPMNs and oPMNs from periodontitis patients, which did not differ significantly from healthy controls. Since cPMNs may acquire a more osteoclastogenesis-facilitating phenotype while migrating into the inflamed periodontium, we next investigated whether stimulated (with LPS, TNF-α, or IL-6) cPMNs have the capacity to contribute to osteoclastogenesis. Enduring surface expression of RANKL for short-lived cells as cPMNs was achieved by fixating stimulated cPMNs. RANKL expression on stimulated cPMNs, as assessed by flow cytometry and immunohistochemistry, was limited (6.48±0.72%, mean expression±SEM) after 24 and 48 hours of stimulation with LPS. Likewise, stimulation with TNF-α and IL-6 resulted in limited RANKL expression levels. These limited levels of expression did not induce osteoclastogenesis when cocultured with preosteoclasts for 10 days. We report that, under the aforementioned experimental conditions, neither cPMNs nor oPMNs directly induced osteoclastogenesis. Further elucidation of the key cellular players and immune mediators that stimulate alveolar bone resorption in periodontitis will help to unravel its pathogenesis.