Gas exchange and chlorophyll fluorescence responses of Camellia sinensis grown under various cultivations in different seasons.

Sod culture (SC) and conventional agriculture (CA) represent two distinct field management approaches utilized in the cultivation of tea plants in Taiwan. In this study, we employed gas exchange and chlorophyll fluorescence techniques to assess the impact of SC and CA methods on the photosynthetic machinery of Camellia sinensis cv. TTES No.12 (Jhinhsuan) in response to variable light intensities across different seasons. In spring, at photosynthetic photon flux densities (PPFD) ranging from 800 to 2,000 µmol photon m-2 s-1, the net photosynthesis rate (Pn, 10.43 µmol CO2 m-2 s-1), stomatal conductance (Gs, 126.11 mmol H2O m-2 s-1), electron transport rate (ETR, 137.94), and ΔF/Fm' and Fv/Fm (50.37) values for plants grown using SC were comparatively higher than those cultivated under CA. Conversely, the non-photochemical quenching (NPQ) values for SC-grown plants were relatively lower (3.11) compared to those grown under CA at 800 to 2,000 PPFD in spring. Additionally, when tea plants were exposed to PPFD levels below 1,500 µmol photon m- 2 s- 1, there was a concurrent increase in Pn, Gs, ETR, and NPQ. These photosynthetic parameters are crucial for devising models that optimize cultivation practices across varying seasons and specific tillage requirements, and for predicting photosynthetic and respiratory responses of tea plants to seasonally or artificially altered light irradiances. The observed positive impacts of SC on maximum photosynthetic rate (Amax), Fv/Fm, Gs, water-use efficiency (WUE), and ETR suggest that SC is advantageous for enhancing the productivity of tea plants, thereby offering a more adaptable management model for tea gardens.

Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR-T cells.

Despite the success of BCMA-targeting CAR-Ts in multiple myeloma, patients with high-risk cytogenetic features still relapse most quickly and are in urgent need of additional therapeutic options. Here, we identify CD70, widely recognized as a favorable immunotherapy target in other cancers, as a specifically upregulated cell surface antigen in high risk myeloma tumors. We use a structure-guided design to define a CD27-based anti-CD70 CAR-T design that outperforms all tested scFv-based CARs, leading to >80-fold improved CAR-T expansion in vivo. Epigenetic analysis via machine learning predicts key transcription factors and transcriptional networks driving CD70 upregulation in high risk myeloma. Dual-targeting CAR-Ts against either CD70 or BCMA demonstrate a potential strategy to avoid antigen escape-mediated resistance. Together, these findings support the promise of targeting CD70 with optimized CAR-Ts in myeloma as well as future clinical translation of this approach.

Low but highly geographically structured genomic diversity of East Asian Eurasian otters and its conservation implications.

Populations of Eurasian otters Lutra lutra, one of the most widely distributed apex predators in Eurasia, have been depleted mainly since the 1950s. However, a lack of information about their genomic diversity and how they are organized geographically in East Asia severely impedes our ability to monitor and conserve them in particular management units. Here, we re-sequenced and analyzed 20 otter genomes spanning continental East Asia, including a population at Kinmen, a small island off the Fujian coast, China. The otters form three genetic clusters (one of L. l. lutra in the north and two of L. l. chinensis in the south), which have diverged in the Holocene. These three clusters should be recognized as three conservation management units to monitor and manage independently. The heterozygosity of the East Asian otters is as low as that of the threatened carnivores sequenced. Historical effective population size trajectories inferred from genomic variations suggest that their low genomic diversity could be partially attributed to changes in the climate since the mid-Pleistocene and anthropogenic intervention since the Holocene. However, no evidence of genetic erosion, mutation load, or high level of inbreeding was detected in the presumably isolated Kinmen Island population. Any future in situ conservation efforts should consider this information for the conservation management units.

Topical Antibiotic Prophylaxis for Preventing Surgical Site Infections of Clean Wounds: A Systematic Review and Meta-Analysis.

Background: Topical antibiotic agents are not generally indicated for preventing of surgical site infections (SSIs) in clean incisions, and the drug concentrations that should be delivered to local incision sites remain uncertain. The aim of this study was to critically assess the efficacy of topical antibiotic agents in comparison with non-antibiotic agents for preventing SSIs in clean incisions by performing a systematic review and meta-analysis. Methods: We conducted a search of literature in PubMed, Embase, and Cochrane Databases and included randomized controlled trials (RCTs) on topical antibiotic use for patients with clean post-surgical incisions. The primary outcome was the incidence of SSI, presented as the event rate. Eleven RCTs were included. Results: Using random-effects modeling, the pooled risk ratio (RR) of developing a post-surgical incisions infection was 0.83 (95% confidence interval [CI], 0.61-1.16; I2, 0%). In subgroup analyses, no reductions in SSI were observed when topical antibiotic agents were used to treat incisions due to spinal (RR, 0.75; 95% CI, 0.40-1.38; I2, 0%), orthopedic (RR, 0.69; 95% CI, 0.37-1.29; I2, 0%), dermatologic (RR, 0.77; 95% CI, 0.39-1.55; I2, 65%), or cardiothoracic surgeries (RR, 1.31; 95% CI, 0.83-2.06; I2: 0%). The incidence of SSI across different operative phases did not differ for the application of topical antibiotic agents compared with non-antibiotic agents (RR, 0.80; 95% CI, 0.56-1.14; I2, 0%). Conclusions: The results of this meta-analysis show that topical antibiotic agents provide no clinical benefit for preventing SSI in clean incisions.

Human APOBEC3B promotes tumor development in vivo including signature mutations and metastases.

The antiviral DNA cytosine deaminase APOBEC3B has been implicated as a source of mutation in many cancers. However, despite years of work, a causal relationship has yet to be established in vivo. Here, we report a murine model that expresses tumor-like levels of human APOBEC3B. Animals expressing full-body APOBEC3B appear to develop normally. However, adult males manifest infertility, and older animals of both sexes show accelerated rates of carcinogenesis, visual and molecular tumor heterogeneity, and metastasis. Both primary and metastatic tumors exhibit increased frequencies of C-to-T mutations in TC dinucleotide motifs consistent with the established biochemical activity of APOBEC3B. Enrichment for APOBEC3B-attributable single base substitution mutations also associates with elevated levels of insertion-deletion mutations and structural variations. APOBEC3B catalytic activity is required for all of these phenotypes. Together, these studies provide a cause-and-effect demonstration that human APOBEC3B is capable of driving both tumor initiation and evolution in vivo.

A CRISPR-engineered isogenic model of the 22q11.2 A-B syndromic deletion.

22q11.2 deletion syndrome, associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided insight into this condition. However, patient-derived iPS cells may harbor underlying genetic heterogeneity that can confound analysis. Furthermore, almost all available models reflect the commonly-found ~ 3 Mb "A-D" deletion at this locus. The ~ 1.5 Mb "A-B" deletion, a variant of the 22q11.2 deletion which may lead to different syndromic features, and is much more frequently inherited than the A-D deletion, remains under-studied due to lack of relevant models. Here we leveraged a CRISPR-based strategy to engineer isogenic iPS models of the 22q11.2 "A-B" deletion. Differentiation to excitatory neurons with subsequent characterization by transcriptomics and cell surface proteomics identified deletion-associated alterations in proliferation and adhesion. To illustrate in vivo applications of this model, we further implanted neuronal progenitor cells into the cortex of neonatal mice and found potential alterations in neuronal maturation. The isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.

Recent Advances in 2D Material Theory, Synthesis, Properties, and Applications.

Two-dimensional (2D) material research is rapidly evolving to broaden the spectrum of emergent 2D systems. Here, we review recent advances in the theory, synthesis, characterization, device, and quantum physics of 2D materials and their heterostructures. First, we shed insight into modeling of defects and intercalants, focusing on their formation pathways and strategic functionalities. We also review machine learning for synthesis and sensing applications of 2D materials. In addition, we highlight important development in the synthesis, processing, and characterization of various 2D materials (e.g., MXnenes, magnetic compounds, epitaxial layers, low-symmetry crystals, etc.) and discuss oxidation and strain gradient engineering in 2D materials. Next, we discuss the optical and phonon properties of 2D materials controlled by material inhomogeneity and give examples of multidimensional imaging and biosensing equipped with machine learning analysis based on 2D platforms. We then provide updates on mix-dimensional heterostructures using 2D building blocks for next-generation logic/memory devices and the quantum anomalous Hall devices of high-quality magnetic topological insulators, followed by advances in small twist-angle homojunctions and their exciting quantum transport. Finally, we provide the perspectives and future work on several topics mentioned in this review.

Human APOBEC3B promotes tumor heterogeneity in vivo including signature mutations and metastases.

The antiviral DNA cytosine deaminase APOBEC3B has been implicated as a source of mutation in many different cancers. Despite over 10 years of work, a causal relationship has yet to be established between APOBEC3B and any stage of carcinogenesis. Here we report a murine model that expresses tumor-like levels of human APOBEC3B after Cre-mediated recombination. Animals appear to develop normally with full-body expression of APOBEC3B. However, adult males manifest infertility and older animals of both sexes show accelerated rates of tumorigenesis (mostly lymphomas or hepatocellular carcinomas). Interestingly, primary tumors also show overt heterogeneity, and a subset spreads to secondary sites. Both primary and metastatic tumors exhibit increased frequencies of C-to-T mutations in TC dinucleotide motifs consistent with the established biochemical activity of APOBEC3B. Elevated levels of structural variation and insertion-deletion mutations also accumulate in these tumors. Together, these studies provide the first cause-and-effect demonstration that human APOBEC3B is an oncoprotein capable of causing a wide range of genetic changes and driving tumor formation in vivo .

Allosteric HSP70 inhibitors perturb mitochondrial proteostasis and overcome proteasome inhibitor resistance in multiple myeloma.

Proteasome inhibitor (PI) resistance remains a central challenge in multiple myeloma. To identify pathways mediating resistance, we first mapped proteasome-associated genetic co-dependencies. We identified heat shock protein 70 (HSP70) chaperones as potential targets, consistent with proposed mechanisms of myeloma cells overcoming PI-induced stress. We therefore explored allosteric HSP70 inhibitors (JG compounds) as myeloma therapeutics. JG compounds exhibited increased efficacy against acquired and intrinsic PI-resistant myeloma models, unlike HSP90 inhibition. Shotgun and pulsed SILAC mass spectrometry demonstrated that JGs unexpectedly impact myeloma proteostasis by destabilizing the 55S mitoribosome. Our data suggest JGs have the most pronounced anti-myeloma effect not through inhibiting cytosolic HSP70 proteins but instead through mitochondrial-localized HSP70, HSPA9/mortalin. Analysis of myeloma patient data further supports strong effects of global proteostasis capacity, and particularly HSPA9 expression, on PI response. Our results characterize myeloma proteostasis networks under therapeutic pressure while motivating further investigation of HSPA9 as a specific vulnerability in PI-resistant disease.

The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.

The myeloma surface proteome (surfaceome) determines tumor interaction with the microenvironment and serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to define the myeloma surfaceome at baseline, in drug resistance, and in response to acute drug treatment. We provide a scoring system for surface antigens and identify CCR10 as a promising target in this disease expressed widely on malignant plasma cells. We engineer proof-of-principle chimeric antigen receptor (CAR) T-cells targeting CCR10 using its natural ligand CCL27. In myeloma models we identify proteins that could serve as markers of resistance to bortezomib and lenalidomide, including CD53, CD10, EVI2B, and CD33. We find that acute lenalidomide treatment increases activity of MUC1-targeting CAR-T cells through antigen upregulation. Finally, we develop a miniaturized surface proteomic protocol for profiling primary plasma cell samples with low inputs. These approaches and datasets may contribute to the biological, therapeutic, and diagnostic understanding of myeloma.

Secretory autophagy maintains proteostasis upon lysosome inhibition.

The endolysosome system plays central roles in both autophagic degradation and secretory pathways, including the release of extracellular vesicles and particles (EVPs). Although previous work reveals important interconnections between autophagy and EVP-mediated secretion, our understanding of these secretory events during endolysosome inhibition remains incomplete. Here, we delineate a secretory autophagy pathway upregulated in response to endolysosomal inhibition, which mediates EVP-associated release of autophagic cargo receptors, including p62/SQSTM1. This secretion is highly regulated and dependent on multiple ATGs required for autophagosome formation, as well as the small GTPase Rab27a. Furthermore, disrupting autophagosome maturation, either via genetic inhibition of autophagosome-to-autolysosome fusion or expression of SARS-CoV-2 ORF3a, is sufficient to induce EVP secretion of autophagy cargo receptors. Finally, ATG-dependent EVP secretion buffers against the intracellular accumulation of autophagy cargo receptors when classical autophagic degradation is impaired. Thus, we propose secretory autophagy via EVPs functions as an alternate route to clear sequestered material and maintain proteostasis during endolysosomal dysfunction or impaired autophagosome maturation.

Range map datasets for terrestrial vertebrates across Taiwan.

Accurate data describing the geographic distribution of specific species form the basis for effective conservation management policies. However, for most species the freely available distributional information is usually confined to either expert maps or purely theoretical maps constructed by using a variety of modeling frameworks. These maps usually do not provide enough resolution for conservation applications or do not accurately describe the current distribution status. In this study, we constructed a novel workflow designed to integrate data from various species distribution models and expert knowledge into a single unified modeling process. Under this workflow, we systematically constructed current distribution maps for a selection of terrestrial vertebrates found across Taiwan. We used species distribution modeling as the base and then aggregated multiple open datasets describing species occurrence and environmental factors as data sources. Thereafter, we estimated the primary broad-scale and high spatial resolution species range maps using the MaxEnt modeling algorithm, and then consulted experts on each taxa to refine these maps. This dataset provides up-to-date species distribution maps for 379 terrestrial vertebrates in Taiwan, with members from across four taxa (27 amphibians, 52 reptiles, 264 birds, and 36 mammals). This dataset helps to fill the spatial knowledge gaps for conservation concerns and improves our understanding of the geographic distribution of more than half (61%) of the vertebrate species of Taiwan. Furthermore, by stacking the range maps of multiple species, we can identify vertebrate diversity hotspots and identify priority areas for conservation.

Differential Acceptance of Advance Directives Between Millennials and Baby Boomer Generations: A Cross-Sectional Survey Study Among College Students and Their Relatives.

Objectives: This study aims to explore the differentials of knowledge and attitude of advance directives (ADs) between millennials and baby boomer generations, and the effects of the intention to sign the advance directives. Methods: This is a cross-sectional study using a self-administered questionnaire to collect data from 325 students in a health-related college of a University of Science and Technology in Taiwan, and their parents, as total of 226, who are baby boomers. The statistical methods include descriptive statistics and inferential statistics. Results: Only 10 people from the 2 generations signed an AD. The multivariate logistic regression showed that baby boomer generation, AD knowledge, and AD attitude were significant positive associate of willingness to sign AD in the future. Conclusions: The government may enhance promotion of ADs among millennials and improve the connection between millennials' knowledge of and attitude toward ADs, and their AD signing behavior.

Larval Morphology of Pit-building Antlions of the Tribe Myrmeleontini (Neuroptera, Myrmeleontidae) from Taiwan.

The larvae of nine species of the pit-building tribe Myrmeleontini from Taiwan are described, belonging to the genera Baliga Navás and Myrmeleon Linnaeus. The nine species can be distinguished from each other by the body markings, mandible chaetotaxy and arrangement of the abdominal digging setae. Additionally, this study is also the first to describe the larvae of M. bimaculatus Yang and the first to report this species in Taiwan. A key to the larvae of nine examined species from Taiwan is provided.

GRASP55 restricts early-stage autophagy and regulates spatial organization of the early secretory network.

There is great interest in understanding the cellular mechanisms controlling autophagy, a tightly regulated catabolic and stress-response pathway. Prior work has uncovered links between autophagy and the Golgi reassembly stacking protein of 55 kDa (GRASP55), but their precise interrelationship remains unclear. Intriguingly, both autophagy and GRASP55 have been functionally and spatially linked to the endoplasmic reticulum (ER)---Golgi interface, broaching this compartment as a site where GRASP55 and autophagy may intersect. Here, we uncover that loss of GRASP55 enhances LC3 puncta formation, indicating that GRASP55 restricts autophagosome formation. Additionally, using proximity-dependent biotinylation, we identify a GRASP55 proximal interactome highly associated with the ER-Golgi interface. Both nutrient starvation and loss of GRASP55 are associated with coalescence of early secretory pathway markers. In light of these findings, we propose that GRASP55 regulates spatial organization of the ER-Golgi interface, which suppresses early autophagosome formation.

A New Photographic Reproduction Method Based on Feature Fusion and Virtual Combined Histogram Equalization.

A desirable photographic reproduction method should have the ability to compress high-dynamic-range images to low-dynamic-range displays that faithfully preserve all visual information. However, during the compression process, most reproduction methods face challenges in striking a balance between maintaining global contrast and retaining majority of local details in a real-world scene. To address this problem, this study proposes a new photographic reproduction method that can smoothly take global and local features into account. First, a highlight/shadow region detection scheme is used to obtain prior information to generate a weight map. Second, a mutually hybrid histogram analysis is performed to extract global/local features in parallel. Third, we propose a feature fusion scheme to construct the virtual combined histogram, which is achieved by adaptively fusing global/local features through the use of Gaussian mixtures according to the weight map. Finally, the virtual combined histogram is used to formulate the pixel-wise mapping function. As both global and local features are simultaneously considered, the output image has a natural and visually pleasing appearance. The experimental results demonstrated the effectiveness of the proposed method and the superiority over other seven state-of-the-art methods.

A Machine Learning-Based Fall Risk Assessment Model for Inpatients.

Falls are one of the most common accidents among inpatients and may result in extended hospitalization and increased medical costs. Constructing a highly accurate fall prediction model could effectively reduce the rate of patient falls, further reducing unnecessary medical costs and patient injury. This study applied data mining techniques on a hospital's electronic medical records database comprising a nursing information system to construct inpatient-fall-prediction models for use during various stages of inpatient care. The inpatient data were collected from 15 inpatient wards. To develop timely and effective fall prediction models for inpatients, we retrieved the data of multiple-time assessment variables at four points during hospitalization. This study used various supervised machine learning algorithms to build classification models. Four supervised learning and two classifier ensemble techniques were selected for model development. The results indicated that Bagging+RF classifiers yielded optimal prediction performance at all four points during hospitalization. This study suggests that nursing personnel should be aware of patients' risk factors based on comprehensive fall risk assessment and provide patients with individualized fall prevention interventions to reduce inpatient fall rates.

A Smart Home Energy Management System Using Two-Stage Non-Intrusive Appliance Load Monitoring over Fog-Cloud Analytics Based on Tridium's Niagara Framework for Residential Demand-Side Management.

Electricity is a vital resource for various human activities, supporting customers' lifestyles in today's modern technologically driven society. Effective demand-side management (DSM) can alleviate ever-increasing electricity demands that arise from customers in downstream sectors of a smart grid. Compared with the traditional means of energy management systems, non-intrusive appliance load monitoring (NIALM) monitors relevant electrical appliances in a non-intrusive manner. Fog (edge) computing addresses the need to capture, process and analyze data generated and gathered by Internet of Things (IoT) end devices, and is an advanced IoT paradigm for applications in which resources, such as computing capability, of a central data center acted as cloud computing are placed at the edge of the network. The literature leaves NIALM developed over fog-cloud computing and conducted as part of a home energy management system (HEMS). In this study, a Smart HEMS prototype based on Tridium's Niagara Framework® has been established over fog (edge)-cloud computing, where NIALM as an IoT application in energy management has also been investigated in the framework. The SHEMS prototype established over fog-cloud computing in this study utilizes an artificial neural network-based NIALM approach to non-intrusively monitor relevant electrical appliances without an intrusive deployment of plug-load power meters (smart plugs), where a two-stage NIALM approach is completed. The core entity of the SHEMS prototype is based on a compact, cognitive, embedded IoT controller that connects IoT end devices, such as sensors and meters, and serves as a gateway in a smart house/smart building for residential DSM. As demonstrated and reported in this study, the established SHEMS prototype using the investigated two-stage NIALM approach is feasible and usable.

Surface Proteomics Reveals CD72 as a Target for In Vitro-Evolved Nanobody-Based CAR-T Cells in KMT2A/MLL1-Rearranged B-ALL.

Alternative strategies are needed for patients with B-cell malignancy relapsing after CD19-targeted immunotherapy. Here, cell surface proteomics revealed CD72 as an optimal target for poor-prognosis KMT2A/MLL1-rearranged (MLLr) B-cell acute lymphoblastic leukemia (B-ALL), which we further found to be expressed in other B-cell malignancies. Using a recently described, fully in vitro system, we selected synthetic CD72-specific nanobodies, incorporated them into chimeric antigen receptors (CAR), and demonstrated robust activity against B-cell malignancy models, including CD19 loss. Taking advantage of the role of CD72 in inhibiting B-cell receptor signaling, we found that SHIP1 inhibition increased CD72 surface density. We establish that CD72-nanobody CAR-T cells are a promising therapy for MLLr B-ALL. SIGNIFICANCE: Patients with MLLr B-ALL have poor prognoses despite recent immunotherapy advances. Here, surface proteomics identifies CD72 as being enriched on MLLr B-ALL but also widely expressed across B-cell cancers. We show that a recently described, fully in vitro nanobody platform generates binders highly active in CAR-T cells and demonstrate its broad applicability for immunotherapy development.This article is highlighted in the In This Issue feature, p. 1861.

Perch time allocation and feeding efficiency of flycatching Rhinolophus formosae: an optimal foraging behavior?

BACKGROUND: Flycatching bats are species-rare and comprise predominantly horseshoe bats (Rhinolophidae). Their hang-and-wait foraging mode and long constant-frequency echolocation calls offer advantages in energetics and prey detection, and may enable them apt to foraging optimally, yet not much is known about the foraging behavior of flycatching bats. Thus we assessed the perch use and foraging performance in the field by one of the largest horseshoe bats, Rhinolophus formosae, and offered insights on their perch time allocation. RESULTS: The perching-foraging behaviors of the bats did not differ significantly between forest settings, but the residence and giving-up time, mean attack, and attack rate were higher in the late spring-early summer, whereas the mean capture, capture rate, and attack efficiency were lower in the late summer when volant juveniles joined the nocturnal activity. The bats maintained flycatching and exhibited largely similar attack rates through the night with peak residence time around the midnight, but the capture rate and attack efficiency both reduced toward midnight and then increased toward the hours right before dawn. The attack rate was negatively correlated to the number of perches used and perch switch; by contrast, the capture rate was positively correlated with both factors. The total residence time at a site increased but mean residence time per perch decreased as the number of perches used and perch-switch increased. The giving-up time was inversely correlated to the attack rate and attack efficiency, and decreased with an increasing capture rate. CONCLUSIONS: The bats increased perch switch at lower attack rates in early spring, but switched less frequently in late spring and prime summer months when insect abundance is higher. By scanning through a broad angular range for prey detection, and switching more frequently among perches, R. formosae foraged with an increased capture rate, and were able to remain at the site longer by slightly reducing their mean residence time per perch. Our results concur with the predictions of optimal foraging theory for patch selection and offer implications for further exploration of the foraging behavior of flycatching horseshoe bats.