Genome-wide CRISPR screenings identified SMCHD1 as a host-restricting factor for AAV transduction.

AAV-mediated gene therapy typically requires a high dose of viral transduction, risking acute immune responses and patient safety, part of which is due to limited understanding of the host-viral interactions, especially post-transduction viral genome processing. Here, through a genome-wide CRISPR screen, we identified SMCHD1 (Structural Maintenance of Chromosomes Hinge Domain 1), an epigenetic modifier, as a critical broad-spectrum restricting host factor for post-entry AAV transgene expression. SMCHD1 knock-down by RNAi and CRISPRi or knock-out by CRISPR all resulted in significantly enhanced transgene expression across multiple viral serotypes, as well as for both single-strand and self-complementary AAV genome types. Mechanistically, upon viral transduction, SMCHD1 effectively repressed AAV transcription by the formation of an LRIF1-HP1-containing protein complex and directly binding with the AAV genome to maintain a heterochromatin-like state. SMCHD1-KO or LRIF1-KD could disrupt such a complex and thus result in AAV transcriptional activation. Together, our results highlight the host factor-induced chromatin remodeling as a critical inhibitory mechanism for AAV transduction and may shed light on further improvement in AAV-based gene therapy.

OTSUCNV: an adaptive segmentation and OTSU-based anomaly classification method for CNV detection using NGS data.

Copy-number variations (CNVs), which refer to deletions and duplications of chromosomal segments, represent a significant source of variation among individuals, contributing to human evolution and being implicated in various diseases ranging from mental illness and developmental disorders to cancer. Despite the development of several methods for detecting copy number variations based on next-generation sequencing (NGS) data, achieving robust detection performance for CNVs with arbitrary coverage and amplitude remains challenging due to the inherent complexity of sequencing samples. In this paper, we propose an alternative method called OTSUCNV for CNV detection on whole genome sequencing (WGS) data. This method utilizes a newly designed adaptive sequence segmentation algorithm and an OTSU-based CNV prediction algorithm, which does not rely on any distribution assumptions or involve complex outlier factor calculations. As a result, the effective detection of CNVs is achieved with lower computational complexity. The experimental results indicate that the proposed method demonstrates outstanding performance, and hence it may be used as an effective tool for CNV detection.

Network Meta-Analysis Indicates Superior Effects of Omega-3 Polyunsaturated Fatty Acids in Preventing the Transition to Psychosis in Individuals at Clinical High-Risk.

BACKGROUND: The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate the efficacy of pharmacological and nutritional interventions in CHR-P and whether these interventions can enhance the efficacy of psychological treatments. METHODS: We systematically reviewed data from 5 databases until July 24, 2021: PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, and WanFang Data. The primary outcome was the transition to psychosis. Network meta-analyses were conducted at 3 time points (6, 12, and ≥24 months) considering both pharmacological/nutritional interventions alone and its combination with psychotherapy. RESULTS: Out of 11 417 identified references, 21 studies were included, comprising 1983 participants. CHR-P participants receiving omega-3 polyunsaturated fatty acids treatment were associated with a lower probability of transition compared with placebo/control at 6 months (odds ratio [OR] = 0.07, 95% confidence interval [CI] = .01 to .054), 12 months (OR = 0.14, 95% CI = .03 to .66), and ≥24 months (OR = 0.16, 95% CI = .05 to .54). Moreover, risperidone plus psychotherapy was associated with a lower likelihood of transition at 6 months compared with placebo/control plus psychotherapy, but this result was not sustained over longer durations. CONCLUSION: Omega-3 polyunsaturated fatty acids helped in preventing transitions to psychosis compared with controls. PROSPERO REGISTRATION NUMBER: CRD42021256209.

Adsorption of LIBs Thermal Runaway Gases on TM-Decorated HfS2 Surface: A DFT Study.

With the wide application of lithium-ion batteries (LIBs) in different fields, safety accidents occur frequently. Therefore, it is necessary to monitor the thermal runaway gas for an early warning. In this article, the adsorption properties of the characteristic gases of LIBs thermal runaway gases are studied by density functional theory (DFT). The adsorption structure of TM (Co/Rh/Ir)-decorated HfS2 (TM@HfS2) is established, and its adsorption properties for C2H4, CH4, and CO are studied. The adsorption energy, charge transfer, band, DOS, charge difference density, work function, and recovery time are discussed in detail. The results show that Ir@HfS2 has the strongest adsorption performance for C2H4 and CO, so C2H4 and CO can be stably adsorbed on the surface of the Ir@HfS2 monolayer. The adsorption energy of CH4 on Co@HfS2 is stronger than those of Rh@HfS2 and Ir@HfS2, but the adsorption energy is still very small. By applying biaxial strain to Co@HfS2, we found that the adsorption energy increases with the increase in negative strain. This study provides a theoretical basis for the regulation of the adsorption properties of HfS2 by different transition metals.

Coulomb blockade and Coulomb staircases in CoBi nanoislands on SrTiO3(001).

We successfully fabricated two-dimensional metallic CoBi nanoislands on SrTiO3(001) substrate by molecular beam epitaxy, and systematically investigated their electronic structures by scanning tunneling microscopy and spectroscopyin situat 4.2 K. Coulomb blockade and Coulomb staircases with discrete and well-separated levels are observed for the individual nanoisland, which is attributed to single-electron tunneling via two tunnel junction barriers. They are in excellent agreement with the simulations based on orthodox theory. Furthermore, we demonstrated that the Coulomb blockade becomes weaker with increasing temperature and almost disappears at ∼22 K in our variable temperature experiment, and its full-width at half-maximum of dI/dVpeaks with temperature is ∼6 mV. Our results provide a new platform for designing single-electron transistors that have potential applications in future microelectronics.

Prediction of Base-Catalyzed Hydrolysis Kinetics of Polychlorinated Dibenzo-p-Dioxins by Density Functional Theory Calculations.

Polychlorinated dibenzo-p-dioxins (PCDDs), comprising 75 congeners, have gained considerable attention from the general public and the scientific community owing to their high toxic potential. The base-catalyzed hydrolysis of PCDDs is crucial for the assessment of their environmental persistence. Nonetheless, owing to the substantial number of congeners and low hydrolysis rates of PCDDs, conducting hydrolysis experiments proves to be exceedingly time-consuming and financially burdensome. Herein, density functional theory and transition state theory were employed to predict the base-catalyzed hydrolysis of PCDDs in aquatic environments. Findings reveal that PCDDs undergo base-catalyzed hydrolysis in aquatic environments with two competing pathways: prevailing dioxin ring-opening and reduced reactivity in the hydrolytic dechlorination pathway. The resultant minor products include hydroxylated PCDDs, which exhibit thermodynamic stability surpassing that of the principal product, chlorinated hydroxydiphenyl ethers. The half-lives (ranging from 17.10 to 1.33 × 1010 h at pH = 8) associated with the base-catalyzed hydrolysis of PCDDs dissolved in water were shorter compared to those within the water-sediment environmental system. This observation implies that hydroxide ions can protect aquatic environments from PCDD contamination. Notably, this study represents the first attempt to predict the base-catalyzed hydrolysis of PCDDs by using quantum chemical methods.

Nitrogen-vacancy-modulated efficient ammonia desorption over 3d TM-anchored BC3N2 monolayer.

Nitrogen fixation using electrochemical methods on the surface of single-atom catalysts (SACs) provides a highly feasible strategy for green and low-energy-consumption ammonia (NH3) production. Herein, using density functional theory (DFT) calculations, we explored in detail the potential of monolayer BC3N2 SACs supported with 3d transition metal (TM) atoms (TM@BC3N2) to facilitate nitrogen reduction. The results revealed that the TM@BC3N2 systems exhibited remarkable catalytic activity in the nitrogen-reduction reaction (NRR). The fine NRR activity was related to the just-right bonding/antibonding orbital interactions between the 2π* of N2 and the d orbitals of the TM ions. The nitrogen-adsorption configurations were found to have different activation mechanisms. In addition, the effects of convectively formed convex nitrogen defects (VN) on the interaction between N2 and VN-TM@BC3N2 and the NRR process of VN-TM@BC3N2 were studied, and it was found that VN could fine-tune the reaction efficiency of the eNRR because after N atom dissociation to form VN, the interaction of TM-C3 was enhanced, and the activation of nitrogen and adsorption of NH3 by the TM-active centers were weakened. The present study can be used as a motivation for further experimental and theoretical research of 2D monolayers as NRR electrocatalysts.

Manoeuvre Target Tracking in Wireless Sensor Networks Using Convolutional Bi-Directional Long Short-Term Memory Neural Networks and Extended Kalman Filtering.

Aiming at the problem that traditional wireless sensor networks produce errors in the positioning and tracking of motorised targets due to noise interference, this paper proposes a motorised target tracking method with a convolutional bi-directional long and short-term memory neural network and extended Kalman filtering, which is trained by using the simulated RSSI value and the actual target value of motorised targets collected from the convolutional bi-directional neural network to the sensor anchor node, so as to obtain a more accurate initial value of the manoeuvre target, and at the same time, the extended Kalman filtering method is used to accurately locate and track the real-time target, so as to obtain the accurate positioning and tracking information of the real-time target. Through experimental simulation, it can be seen that the algorithm proposed in this paper has good tracking effect in both linear manoeuvre target tracking scenarios and non-linear manoeuvre target tracking scenarios.

Camera-Based Dynamic Vibration Analysis Using Transformer-Based Model CoTracker and Dynamic Mode Decomposition.

Accelerometers are commonly used to measure vibrations for condition monitoring in mechanical and civil structures; however, their high cost and point-based measurement approach present practical limitations. With rapid advancements in computer vision and deep learning, research into tracking the motion of individual pixels with vision cameras has increased. The recently developed CoTracker, a transformer-based model, has demonstrated excellence in motion tracking, yet its performance in measuring structural vibrations has not been fully explored. This paper investigates the efficacy of the CoTracker model in extracting full-field structural vibrations using cameras. It is initially applied to capture the dense point movements in video sequences of a cantilever beam recorded using a high-speed camera. Subsequently, modal analysis using delay-embedding dynamic mode decomposition (DMD) is conducted to extract modal parameters including natural frequencies, damping ratios, and mode shapes. The results, benchmarked against those from a reference accelerometer and the Finite Element Method (FEM) result, demonstrate CoTracker's high potential for general applicability in structural vibration measurements.

Compensatory Genetic and Transcriptional Cytonuclear Coordination in Allopolyploid Lager Yeast (Saccharomyces pastorianus).

Cytonuclear coordination between biparental-nuclear genomes and uniparental-cytoplasmic organellar genomes in plants is often resolved by genetic and transcriptional cytonuclear responses. Whether this mechanism also acts in allopolyploid members of other kingdoms is not clear. Additionally, cytonuclear coordination of interleaved allopolyploid cells/individuals within the same population is underexplored. The yeast Saccharomyces pastorianus provides the opportunity to explore cytonuclear coevolution during different growth stages and from novel dimensions. Using S. pastorianus cells from multiple growth stages in the same environment, we show that nuclear mitochondria-targeted genes have undergone both asymmetric gene conversion and growth stage-specific biased expression favoring genes from the mitochondrial genome donor (Saccharomyces eubayanus). Our results suggest that cytonuclear coordination in allopolyploid lager yeast species entails an orchestrated and compensatory genetic and transcriptional evolutionary regulatory shift. The common as well as unique properties of cytonuclear coordination underlying allopolyploidy between unicellular yeasts and higher plants offers novel insights into mechanisms of cytonuclear evolution associated with allopolyploid speciation.

EIF3H stabilizes CCND1 to promotes intrahepatic cholangiocarcinoma progression via Wnt/ß-catenin signaling.

Cholangiocarcinoma (CCA) is a group of tumors that arise along the human biliary duct tree, ranking second in primary hepatic malignancies. Intrahepatic CCA (iCCA) represents about 10%-20% of CCAs. There is an increasing body of evidence suggesting that iCCAs' incidence and mortality have been increasing globally over the past few decades. In this study, we found that the EIF3H expression level in iCCA tissues was significantly increased compared to the adjacent non-cancerous tissues by immunohistochemistry analysis (IHC). A similar tendency of EIF3H mRNA and protein level was confirmed in iCCA cell lines using RT-qPCR and Western blot. EIF3H has been identified as a critical molecule that plays a pro-neoplasmic role in iCCA both in vivo and in vitro, such as proliferation, migration, and anti-apoptosis. Mechanistically, we found that EIF3H knockdown can promote the degradation of CCND1 and the proteolysis of CCND1 is mediated by ubiquitin-proteasome system (UPS). Thus, we come to the conclusion that EIF3H promotes proliferation and migration of iCCAs, inhibiting apoptosis of iCCA cells at the same time by stabilizing the CCND1 protein structure. Our findings provide insights into the mechanism of tumorigenesis role of EIF3H in iCCAs and a potential therapeutic target for iCCA treatment.

Adsorption and Gas-Sensing Performance of the Small-Molecule Gas on ZrSe2 Monolayers: A First-Principles Study.

The adsorption of five small gas molecules (CO, CO2, NO, NO2, and NH3) on transition metal (TM)-modified ZrSe2 monolayers (Au-ZrSe2 and Pt-ZrSe2) are studied based on first principles. The adsorption structure, adsorption energy (Eads), electron transfer (Qt), and density of states (DOS) with intrinsic ZrSe2, Au-ZrSe2, and Pt-ZrSe2 monolayers are discussed, and their sensing performance is evaluated. The results show that the electrical conductivity of ZrSe2 is obviously increased after Au and Pt atom modification. The intrinsic ZrSe2 adsorbs the five kinds of gas molecules weakly, while ZrSe2 modified by the Au or Pt atom improves the adsorption of the gas molecules in different degrees. Au-ZrSe2 has the best adsorption effect on NO2 gas molecules, while Pt-ZrSe2 shows strong sensitivity to CO gas molecules. Moreover, Au-ZrSe2 and Pt-ZrSe2 are of great significance for the adsorption sensing mechanism and also offer prospective materials for the advancement of gas-sensitive sensors.

First-principles study on the catalytic performance of transition metal atom-doped CrSe2 for the oxygen reduction reaction.

Since the oxygen reduction reaction (ORR) is the cathodic reaction of energy storage and conversion devices such as fuel cells and metal-air batteries, the search for catalysts with high-performance toward ORR has become the focus of attention. Transition metal dichalcogenides (TMDs) have the advantages of easy integration, inexpensive, harmless, good stability, and have vast application prospects in stabilizing the single atom. Hence, in this study, we investigated the feasibility of several 4d/5d single transition metals (TM = Rh, Pd, Ag, Ir, Pt, and Au) doped with CrSe2 for ORR electrocatalysis on the basis of density functional theory (DFT) calculations. Our results demonstrated that most of the TM-doped systems are stable, exhibiting metal conductivity, and can well activate the adsorbed O2. Interestingly, compared with end-on adsorption configuration, O2 is more likely to be adsorbed on the catalysts by a side-on adsorption configuration. Among all the candidate ORR catalysts, Pd-doped and Pt-doped CrSe2 have the best catalytic performance with a low overpotential of 0.43 and 0.50 V, respectively, making them good ORR candidate high performance catalysts. Our DFT work helps to understand the interaction between the O2 molecule and transition metal single atoms on CrSe2 supports and provides ideas for designing stable and efficient ORR catalysts.

Adsorption properties of small gas molecules on SnSe2 monolayer supported with transition metal: first-principles calculations.

The adsorption properties of CH4, H2S, SO2, CO, H2O and NO molecules on transition metal-supported SnSe2 surface are investigated by the first-principles method. The calculation results show that the transition metal (TM = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu) has the lowest adsorption energy when supporting at the Sn site of SnSe2, indicating the system is relatively stable. Also, we find that CH4, SO2 and H2O molecules tend to adsorb on Sc-supported SnSe2 surface, H2S and NO molecules prefer to adsorb on V-supported SnSe2 surface, while CO molecule and Fe-supported SnSe2 surfaces have strong interaction. And, CH4, H2S and H2O molecules act as donors to provide electrons to the substrate, while SO2, CO and NO molecules act as acceptors to gain electrons from the substrate. An analysis of charge difference density and density of states reveals that the adsorption energies of gas molecules are related to charge transfer and orbital hybridization. We hope that this work not only provides a promising sensor material, but also provides a new idea for the rational design of two-dimensional materials.

Fe, N, S co-doped cellulose paper carbon fibers as an air-cathode catalyst for microbial fuel cells.

The heteroatoms and transition metal co-doped carbon-based catalysts are an important way to improve the catalytic activity of oxygen reduction reaction (ORR). Herein, we reported a facile method to obtain iron, nitrogen, and sulfur co-doped cellulose paper carbon fibers as catalysts (Fe-N-S/CFs) for ORR in microbial fuel cells (MFCs) with the adsorption recovery of Congo red molecules from dye wastewater. The thermal treatment promoted the etching of carbon surface by ferric ions, resulting in increased surface roughness for forming the defective carbon structure. The rich active species and defective carbon formed on the etched surface to enhance the electroactive surface area and effective sites. Fe-N-S/CFs catalysts achieved high half-wave potential due to the synergy effect between chemical components and defect structures. The assembled single-chamber air cathode MFC gained a high maximum power density of 1773 ± 40 mW m-2 versus Pt/C MFC of 1325 ± 94 mW m-2. This work provides a strategy for recovering dye molecules from wastewater to prepare non-precious metal catalysts for enhancing ORR activity.

Functional analysis of the OsNPF4.5 nitrate transporter reveals a conserved mycorrhizal pathway of nitrogen acquisition in plants.

Low availability of nitrogen (N) is often a major limiting factor to crop yield in most nutrient-poor soils. Arbuscular mycorrhizal (AM) fungi are beneficial symbionts of most land plants that enhance plant nutrient uptake, particularly of phosphate. A growing number of reports point to the substantially increased N accumulation in many mycorrhizal plants; however, the contribution of AM symbiosis to plant N nutrition and the mechanisms underlying the AM-mediated N acquisition are still in the early stages of being understood. Here, we report that inoculation with AM fungus Rhizophagus irregularis remarkably promoted rice (Oryza sativa) growth and N acquisition, and about 42% of the overall N acquired by rice roots could be delivered via the symbiotic route under N-NO3- supply condition. Mycorrhizal colonization strongly induced expression of the putative nitrate transporter gene OsNPF4.5 in rice roots, and its orthologs ZmNPF4.5 in Zea mays and SbNPF4.5 in Sorghum bicolor OsNPF4.5 is exclusively expressed in the cells containing arbuscules and displayed a low-affinity NO3- transport activity when expressed in Xenopus laevis oocytes. Moreover, knockout of OsNPF4.5 resulted in a 45% decrease in symbiotic N uptake and a significant reduction in arbuscule incidence when NO3- was supplied as an N source. Based on our results, we propose that the NPF4.5 plays a key role in mycorrhizal NO3- acquisition, a symbiotic N uptake route that might be highly conserved in gramineous species.

A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis.

NOD-like receptors (NLRs) are traditionally recognized as major inflammasome components. The role of NLRs in germ cell differentiation and reproduction is not known. Here, we identified the gonad-specific Nlrp14 as a pivotal regulator in primordial germ cell-like cell (PGCLC) differentiation in vitro. Physiologically, knock out of Nlrp14 resulted in reproductive failure in both female and male mice. In adult male mice, Nlrp14 knockout (KO) inhibited differentiation of spermatogonial stem cells (SSCs) and meiosis, resulting in trapped SSCs in early stages, severe oligozoospermia, and sperm abnormality. Mechanistically, NLRP14 promoted spermatogenesis by recruiting a chaperone cofactor, BAG2, to bind with HSPA2 and form the NLRP14-HSPA2-BAG2 complex, which strongly inhibited ChIP-mediated HSPA2 polyubiquitination and promoted its nuclear translocation. Finally, loss of HSPA2 protection and BAG2 recruitment by NLRP14 was confirmed in a human nonsense germline variant associated with male sterility. Together, our data highlight a unique proteasome-mediated, noncanonical function of NLRP14 in PGCLC differentiation and spermatogenesis, providing mechanistic insights of gonad-specific NLRs in mammalian germline development.

First Report of Lasiodiplodia theobromae Causing Stem Brown Rot of Loquat in China.

Loquat (Rhaphiolepis biabas, heterotypic synonym: Eriobotrya japonica) is an important edible and medicinal plant that is widely cultivated on 133 thousand hectares (recorded in 2022) in China. A stem brown rot was observed on young and old trees in Mengzi city (23°23' N; 103°23' E), Yunnan Province, southwest China, during October 2014 and September 2021. Incidence ranged from 20% of trees in surrounding plantations to 50% incidence of a 160 tree orchard that was the focal point of the disease survey. Circular brown lesions occurred initially on the stems and gradually covered all the epidermis of the stem, leading to irregular dents within the bark that developed a dark brown powdery appearance (Fig.1A). Larger lesions affected vascular tissues, causing diseased trees to wither and die. Diseased tissues were surface-disinfected in a 5% sodium hypochlorite solution for 3 min, rinsed three times with sterile distilled water, placed on potato dextrose agar (PDA), and incubated in the dark at 28°C. Twenty samples were collected for tissue isolation, and 11 isolates were single-spored on water agar. In culture, the colonies on PDA were white to dark-gray, velvet, with dense hyphae, diameter 7.64 cm after 5 days. After 18 days, spherical or subglobose pycnidia were developed and semi-buried in medium, their walls were thicker and dark-brown, which were black particles surrounded by gray-black hyphae. Conidiogenous cells were hyaline, cylindrical, holoblastic, slightly swollen at the base, with rounded apex. Conidia were initially hyaline and aseptate with elliptic or ovate shape, becoming dark brown with a single septate and developing longitudinal striations along thick walls at maturity. Conidia dimensions varied from 8.0 to 12.2 × 3.8 to 6.1µm (n=50) (Fig.1D). The morphological characteristics of eleven isolates were consistent with the description of Lasiodiplodia theobromae (Alves et al. 2008). Further confirmation was also determined by sequencing the internal transcribed spacer (ITS), ß-tubulin genes, partial translation elongation factor-1α (TEF-1α) (White et al. 1990, Carbone et al. 1999, Glass et al.1995). The isolate LSB-1 was selected for DNA sequence analysis. Based on BLASTn analysis, ITS sequences (OM617921) had 98.3% similarity with L. theobromae CBS164.96 (accession AY640255), CBS124.13(accession DQ458890), CAA006 (accession DQ458891) and CBS111530 (accession EF622074), ß-tubulin sequences (OM643838) showed 99.1% similarity with L. theobromae accessions EU673110. The TEF-1α (OM643839) had 99.0% identity with L. theobromae accession EF633054. The isolate LSB-1 clustered on the same clade with other L. theobromae. Pathogenicity testing of isolate LSB-1, LSB-2, LSB-3 was conducted by inoculating the stems of l-year-old seedlings growing in pots. The epidermis at the inoculation site, 15-20 cm below the crown, was wiped with 75% alcohol cotton ball, washed three times with sterile water, and then punctured (5mm diameter) with sterile inoculation needle. A 5mm block of each isolate cultured on PDA for seven days was attached to the inoculation site. Controls were inoculated with sterile PDA blocks. The inoculation area was covered with polyethylene cling film. All inoculated seedlings were kept in controlled greenhouse at 27°C with 80% relative humidity under natural daylight conditions, and watered weekly. Each treatment was repeated three times. Eight days after inoculation, all diseased plants showed dark brown discoloration at the point of inoculation (Fig. 1G) with the bark at the inoculation site gradually raising as the disease progressed. Thirty days after inoculation, all inoculated seedlings produced typical symptoms, whereas the control seedlings remained healthy. Fungal isolates were only recovered from symptomatic stems and were morphologically identical to L. theobromae, completing Koch's postulates. According to the relevant literature, Lasiodiplodia theobromae has a broad host range, causing numerous diseases, including canker and dieback of branch (Aguilera-Cogley et al., 2021), panicle blight (Mahadevakumar et al, 2022), root rot (Abd-El Ghani and Fatouh, 2005), fruit rot(Freire et al., 2011) in diverse geographical regions. To our knowledge, this is the first report of L. theobromae causing stem brown rot of loquat in China and provides a foundation for further study of the epidemiology and integrated management of this disease.

Post Take-Over Performance Varies in Drivers of Automated and Connected Vehicle Technology in Near-Miss Scenarios.

OBJECTIVE: This study examined the impact of monitoring instructions when using an automated driving system (ADS) and road obstructions on post take-over performance in near-miss scenarios. BACKGROUND: Past research indicates partial ADS reduces the driver's situation awareness and degrades post take-over performance. Connected vehicle technology may alert drivers to impending hazards in time to safely avoid near-miss events. METHOD: Forty-eight licensed drivers using ADS were randomly assigned to either the active driving or passive driving condition. Participants navigated eight scenarios with or without a visual obstruction in a distributed driving simulator. The experimenter drove the other simulated vehicle to manually cause near-miss events. Participants' mean longitudinal velocity, standard deviation of longitudinal velocity, and mean longitudinal acceleration were measured. RESULTS: Participants in passive ADS group showed greater, and more variable, deceleration rates than those in the active ADS group. Despite a reliable audiovisual warning, participants failed to slow down in the red-light running scenario when the conflict vehicle was occluded. Participant's trust in the automated driving system did not vary between the beginning and end of the experiment. CONCLUSION: Drivers interacting with ADS in a passive manner may continue to show increased and more variable deceleration rates in near-miss scenarios even with reliable connected vehicle technology. Future research may focus on interactive effects of automated and connected driving technologies on drivers' ability to anticipate and safely navigate near-miss scenarios. APPLICATION: Designers of automated and connected vehicle technologies may consider different timing and types of cues to inform the drivers of imminent hazard in high-risk scenarios for near-miss events.

Macrophage-Related Testicular Inflammation in Individuals with Idiopathic Non-Obstructive Azoospermia: A Single-Cell Analysis.

Male infertility is a global issue that seriously affects reproductive health. This study aimed to understand the underlying causes of idiopathic non-obstructive azoospermia (iNOA), which is a type of male infertility with unknown origins that accounts for 10-15% of cases. By using single-cell analysis techniques, we aimed to uncover the mechanisms of iNOA and gain insight into the cellular and molecular changes in the testicular environment. In this study, we performed bioinformatics analysis using scRNA-seq and microarray data obtained from the GEO database. The analysis included techniques such as pseudotime analysis, cell-cell communication, and hdWGCNA. Our study showed a significant difference between the iNOA and the normal groups, indicating a disorder in the spermatogenic microenvironment in iNOA. We observed a reduction in the proportion of Sertoli cells and blocked germ cell differentiation. Additionally, we found evidence of testicular inflammation related to macrophages and identified ODF2 and CABYR as potential biomarkers for iNOA.