Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Sirt1 m6A modification-evoked Leydig cell senescence promotes Cd-induced testosterone decline.

Diminished testosterone levels have been documented as a key factor in numerous male health disorders. Both human and animal studies have consistently demonstrated that cadmium (Cd), a pervasive environmental heavy metal, results in decreased testosterone levels. However, the exact mechanism through which Cd interferes with testosterone synthesis remains incompletely elucidated. This research sought to examine the impact of cellular senescence on Cd-suppressed testosterone synthesis. We also investigated the related m6A modification mechanism. The results demonstrated that Cd (100 mg/L) led to a decrease in testosterone levels, along with downregulated expression of testosterone synthase in C57BL/6 N male mice. Furthermore, Cd significantly increased ß-galactosidase staining intensity, senescence-related proteins, and senescence-related secretory phenotypes in mouse testicular Leydig cells. Subsequent investigations revealed that Cd decreased the mRNA and protein levels of NAD-dependent deacetylase Sirtuin-1 (SIRT1) in Leydig cells. Mechanistically, mice treated with resveratrol (50 mg/kg), a specific SIRT1 activator, mitigated Leydig cell senescence and reversed Cd-reduced testosterone levels in mouse testes. These effects were also restored by SIRT1 overexpression in Leydig cells. Additionally, we found that Cd increased the level of methyltransferase enzyme METTL3 and Sirt1 m6A modification in Leydig cells. Mettl3 siRNA effectively restored Cd-enhanced Sirt1 m6A level and reversed Cd-downregulated Sirt1 mRNA expression in Leydig cells. Overall, our findings suggest that Cd exposure inhibits testosterone synthesis via Sirt1 m6A modification-mediated senescence in mouse testes. These results offer an experimental basis for investigating the causes and potential treatments of hypotestosteronemia induced by environmental factors.

Assessing the accuracy of self-reported health expenditure data: Evidence from two public surveys in China.

This paper utilizes Benford's law, the distribution that the first significant digit of numbers in certain datasets should follow, to assess the accuracy of self-reported health expenditure data known for measurement errors. We provide both simulation and real data evidence supporting the validity assumption that genuine health expenditure data conform to Benford's law. We then conduct a Benford analysis of health expenditure variables from two widely utilized public datasets, the China Health and Nutrition Survey and the China Family Panel Studies. Our findings show that health expenditure data in both datasets exhibit inconsistencies with Benford's law, with the former dataset tending to be less prone to reporting errors. These results remain robust while accounting for variations in survey design, recall periods, and sample sizes. Moreover, we demonstrate that data accuracy improves with a shorter time interval between hospitalization and interviews, when the data is self-reported as opposed to proxy responses, and at the household level. We find no compelling evidence that enumerators' assessments of respondents' credibility or urgency to end interviews are indicative of data accuracy. This paper contributes to literature by introducing an easy-to-implement analytical framework for scrutinizing and comparing the reporting accuracy of health expenditure data.

The deflection of fatigued neck.

The human neck is a unique mechanical structure, highly flexible but fatigue prone. The rising prevalence of neck pain and chronic injuries has been attributed to increasing exposure to fatigue loading in activities such as prolonged sedentary work and overuse of electronic devices. However, a causal relationship between fatigue and musculoskeletal mechanical changes remains elusive. This work aimed to establish this relationship through a unique experiment design, inspired by a cantilever beam mechanical model of the neck, and an orchestrated deployment of advanced motion-force measurement technologies including dynamic stereo-radiographic imaging. As a group of 24 subjects performed sustained-till-exhaustion neck exertions in varied positions-neutral, extended, and flexed, their cervical spine musculoskeletal responses were measured. Data verified the occurrence of fatigue and revealed fatigue-induced neck deflection which increased cervical lordosis or kyphosis by 4-5° to 11°, depending on the neck position. This finding and its interpretations render a renewed understanding of muscle fatigue from a more unified motor control perspective as well as profound implications on neck pain and injury prevention.

Dynamic responses of soil microbial communities to seasonal freeze-thaw cycles in a temperate agroecosystem.

Soil freeze-thaw cycles (FTCs) are common in temperate agricultural ecosystems during the non-growing season and are progressively influenced by climate change. The impact of these cycles on soil microbial communities, crucial for ecosystem functioning, varies under different agricultural management practices. Here, we investigated the dynamic changes in soil microbial communities in a Mollisol during seasonal FTCs and examined the effects of stover mulching and nitrogen fertilization. We revealed distinct responses between bacterial and fungal communities. The dominant bacterial phyla reacted differently to FTCs: for example, Proteobacteria responded opportunistically, Actinobacteria, Acidobacteria, Choroflexi and Gemmatimonadetes responded sensitively, and Saccharibacteria exhibited a tolerance response. In contrast, the fungal community composition remained relatively stable during FTCs, except for a decline in Glomeromycota. Certain bacterial OTUs acted as sensitive indicators of FTCs, forming keystone modules in the network that are closely linked to soil carbon, nitrogen content and potential functions. Additionally, neither stover mulching nor nitrogen fertilization significantly influenced microbial richness, diversity and potential functions. However, over time, more indicator species specific to these agricultural practices began to emerge within the networks and gradually occupied the central positions. Furthermore, our findings suggest that farming practices, by introducing keystone microbes and changing interspecies interactions (even without changing microbial richness and diversity), can enhance microbial community stability against FTC disturbances. Specifically, higher nitrogen input with stover removal promotes fungal stability during soil freezing, while lower nitrogen levels increase bacterial stability during soil thawing. Considering the fungal tolerance to FTCs, we recommend reducing nitrogen input for manipulating bacterial interactions, thereby enhancing overall microbial resilience to seasonal FTCs. In summary, our research reveals that microbial responses to seasonal FTCs are reshaped through land management to support ecosystem functions under environmental stress amid climate change.

Hot air treatment alleviates chilling injury of sweet potato tuberous roots by regulating osmoregulatory substances and inducing antioxidant defense system.

Sweet potato tuberous roots are susceptible to chilling injury (CI) when stored below 10 °C. In this study, we investigated the mitigating effects of hot air (HA) treatment on CI. Results showed that HA45°C-3h treatment delayed the CI and internal browning during cold storage. After HA45°C-3h treatment, the cells' structural integrity was maintained, malondialdehyde accumulation and ion leakage were inhibited. Additionally, the osmoregulatory substances, such as total soluble solids, proline were maintained, and soluble protein was enhanced. Higher activity of antioxidant enzymes including superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase, and the antioxidant substances including ascorbic acid, glutathione, total phenols, and flavonoids were observed in sweet potato tuberous roots treated by HA45°C-3h than untreated group. Our study suggested that HA45°C-3h treatment could reduce CI and maintain a better quality of sweet potato tuberous roots following cold storage.

Additional organic and bacterium fertilizer input regulated soybean root architecture and dry matter distribution for a sustainable yield in the semi-arid Region of China.

In the dryland area of the Loess Plateau in northwest China, long-term excessive fertilization has led to soil compaction and nutrient loss, which in turn limits crop yield and soil productivity. To address this issue, we conducted experiments using environmentally friendly organic fertilizer and bacterium fertilizer. Our goal was to investigate the effects of additional organic and bacterium fertilizer inputs on soil water migration, crop root architecture, and yield formation. We implemented six different fertilizer strategies, namely: Nm (mulching, N 30 kg/ha), NPK1m (mulching, N 60 kg/ha; P 30 kg/ha; K 30 kg/ha), NPK2m (mulching, N 90 kg/ha; P 45 kg/ha; K 30 kg/ha), NPKOm (mulching, N 90 kg/ha; P 45 kg/ha; K 30 kg/ha; organic fertilizer 2 t/ha), NPKBm (mulching, N 60 kg/ha; P 30 kg/ha; K 30 kg/ha; bacterium fertilizer 10 kg/ha), and N (N 30 kg/ha; no mulching). The results revealed that the addition of bacterium fertilizer (NPKBm) had a positive impact on soybean root system development. Compared with the other treatments, it significantly increased the total root length, total root surface area, and total root length density by 25.96% ~ 94.89%, -19.63% ~ 36.28%, and 9.36% ~ 28.84%, respectively. Furthermore, NPKBm enhanced soil water consumption. In 2018, water storage during the flowering and podding periods decreased by 12.63% and 19.65%, respectively, while water consumption increased by 0.97% compared to Nm. In 2019, the flowering and harvest periods decreased by 23.49% and 11.51%, respectively, while water consumption increased by 0.65%. Ultimately, NPKBm achieved high grain yield and significantly increased water use efficiency (WUE), surpassing other treatments by 76.79% ~ 78.97% and 71.22% ~ 73.76%, respectively. Subsequently, NPK1m also exhibited significant increases in yield and WUE, with improvements of 35.58% ~ 39.27% and 35.26% ~ 38.16%, respectively. The use of bacterium fertilizer has a profound impact on soybean root architecture, leading to stable and sustainable grain yield production.

Identification and phylogenetic analysis of Nairobi sheep disease virus from Haemaphysalis longicornis ticks in Shandong Province, China.

Nairobi Sheep Disease (NSD) is a typical tick-borne syndrome characterized by severe hemorrhagic gastroenteritis, spontaneous abortion, and a high case fatality rate in small ruminants. The pathogenic agent, Nairobi sheep disease virus (NSDV), has also been associated with human infections, indicating its possible zoonotic potential. Prior to this study, NSDV has been detected from ticks collected in Jilin, Hubei, and Liaoning provinces in China. In the present study, a total of 343 ticks (Haemaphysalis longicornis) were collected in Shandong province, China in 2020, and pooled into 16 libraries. Analysis of the meta-transcriptomic sequencing data identified NSDV strains SDWL07, SDWL08, and SDWL16 from three pools. The SDWL07 and SDWL16 strains were detected from unfed ticks, while SDWL08 was detected from cattle-feeding ticks. Phylogenetic analyses showed higher sequence identities between the three strains and other Chinese NSDV strains than those from India and Kenya. Phylogenetic analyses also revealed that they clustered together and fell within the China lineage, suggesting no potential genetic reassortment among them. In summary, this is the first report of the identification of NSDV in Shandong province, highlighting the continually expanding endemic regions of this pathogen. Surveillance of NSDV should be intensified in China, especially in areas where H. longicornis is endemic.

Midpoint transverse process to pleura block for postoperative analgesia following laparoscopic renal cyst decortication: Two case reports.

BACKGROUND: The midpoint transverse process to pleura (MTP) block, a novel technique for thoracic paravertebral block (TPVB), was first employed in laparoscopic renal cyst decortication. CASE SUMMARY: Thoracic paravertebral nerve block is frequently employed for perioperative analgesia during laparoscopic cyst decortication. To address safety concerns associated with TPVBs, we administered MTP blocks in two patients prior to administering general anesthesia for laparoscopic cyst decortication. The MTP block was performed at the T9 level under ultrasound guidance, with 20 mL of 0.5% ropivacaine injected. Reduced sensation to cold and pinprick was observed from the T8 to T11 dermatome levels. Immediately postoperative Numeric Pain Rating Scale scores were 0/10 at rest and on movement, with none exceeding a mean 24 h numeric rating scale > 3. CONCLUSION: MTP block was effective technique for providing postoperative analgesia for patients undergoing laparoscopic renal cyst decortication.

Greenhouse gas emissions from the growing season are regulated by precipitation events in conservation tillage farmland ecosystems of Northeast China.

Reducing greenhouse gas (GHG) emissions from agricultural ecosystems is vital to mitigate global warming. Conservation tillage is widely used in farmland management to improve soil quality; however, its effects on soil GHG emissions remain poorly understood, particularly in high-yield areas. Therefore, our study aimed to evaluate the effects of no-tillage (NT) combined with four straw-mulching levels (0 %, 33 %, 67 %, and 100 %) on GHG emission risk and the main influencing factors. We conducted in-situ observations of GHG emissions from soils under different management practices during the maize-growing season in Northeastern China. The results showed that NT0 (705.94 g m-2) reduced CO2 emissions by 18 % compared to ridge tillage (RT, 837.04 g m-2). Different straw mulching levels stimulated N2O emissions after rainfall, particularly under NT combined with 100 % straw mulching (2.89 kg ha-1), which was 45 % higher than that in any other treatments. The CH4 emissions flux among different treatments was nearly zero. Overall, straw mulching levels had no significant effect on the GHG emissions. During the growing season, soil NH4+-N (< 20 mg kg-1) remained low and decreased with the extension of growth stage, whereas soil NO3--N initially increased and then decreased. More importantly, the results of structural equation modeling indicate that: a) organic material input and soil moisture are key factors affecting CO2 emissions, b) nitrogen fertilizer and soil moisture promote N2O emissions, and c) climatic factors exert an inexorable influence on the GHG emissions process. Our conclusions emphasize the necessity of incorporating precipitation-response measures into farmland management to reduce the risk of GHG emissions.

A case study of a bispecific antibody manufacturability assessment and optimization during discovery stage and its implications.

The manufacturability assessment and optimization of bispecific antibodies (bsAbs) during the discovery stage are crucial for the success of the drug development process, impacting the speed and cost of advancing such therapeutics to the Investigational New Drug (IND) stage and ultimately to the market. The complexity of bsAbs creates challenges in employing effective evaluation methods to detect developability risks in early discovery stage, and poses difficulties in identifying the root causes and implementing subsequent engineering solutions. This study presents a case of engineering a bsAb that displayed a normal solution appearance during the discovery phase but underwent significant precipitation when subjected to agitation stress during 15 L Chemistry, Manufacturing, and Control (CMC) production Leveraging analytical tools, structural analysis, in silico prediction, and wet-lab validations, the key molecular origins responsible for the observed precipitation were identified and addressed. Sequence engineering to reduce protein surface hydrophobicity and enhance conformational stability proved effective in resolving agitation-induced aggregation. The refined bsAb sequences enabled successful mass production in CMC department. The findings of this case study contribute to the understanding of the fundamental mechanism of agitation-induced aggregation and offer a potential protein engineering procedure for addressing similar issues in bsAb. Furthermore, this case study emphasizes the significance of a close partnership between Discovery and CMC teams. Integrating CMC's rigorous evaluation methods with Discovery's engineering capability can facilitate a streamlined development process for bsAb molecules.

A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase.

Aim: This multicenter retrospective study aimed to develop a novel prognostic system for extranodal natural killer/T-cell lymphoma (ENKTL) patients in the era of pegaspargase/L-asparaginase. Materials & methods: A total of 844 newly diagnosed ENKTL patients were included. Results: Multivariable analysis confirmed that Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL (CA) system, and albumin were independent prognostic factors. By rounding up the hazard ratios from four significant variables, a maximum of 7 points were assigned. The model of Huaihai Lymphoma Working Group-Natural killer/T-cell Lymphoma prognostic index (NPI) was identified with four risk groups and the 5-year overall survival was 88.2, 66.7, 54.3 and 30.5%, respectively. Conclusion: Huaihai Lymphoma Working Group-NPI provides a feasible stratification system for patients with ENKTL in the era of pegaspargase/L-asparaginase.

[Box: see text].

Association of ambient PM2.5 and its components with in vitro fertilization outcomes: The modifying role of maternal dietary patterns.

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the "Fruits-Vegetables-Dairy" pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the "Puffed food-Bakery-Candy" pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the "Grains-Tubers-Legumes". Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.

Mixing due to Solution Switch Limits the Performance of Electrosorption for Desalination.

Electrosorption (ES) is a research frontier in electrochemical separation, with proven potential applications in desalination, wastewater treatment, and selective resource extraction. However, due to the limited adsorption capacity of film electrodes, ES requires short circuiting or circuit reversal, accompanied by a solution switch between the feed solution and receiving solution, to sustain desalination over many charge-discharge cycles. In previously reported studies, solution switches have been commonly ignored to simplify experimental procedures, and their impacts on separation performance are thus not well understood. This study aims to provide a quantitative analysis of the impacts of mixing due to a solution switch on the performance of ES-based desalination. A numerical model of ES has been employed to evaluate the adverse effects of the solution switch on the desalination performance in three commonly used operation modes. The analysis reveals that the impacts of mixing due to solution-switch are more severe with a larger concentration difference between the desalinated water and the brine and provides insights into the effectiveness of increasing electrode loading or specific capacity in mitigating the detrimental impacts of mixing. Even with state-of-the-art systems, producing freshwater from seawater or even brackish water with medium-to-high salinity is practically challenging due to the presence of solution switch.

HSADab: A comprehensive database for human serum albumin.

Human Serum Albumin (HSA), the most abundant protein in human body fluids, plays a crucial role in the transportation, absorption, metabolism, distribution, and excretion of drugs, significantly influencing their therapeutic efficacy. Despite the importance of HSA as a drug target, the available data on its interactions with external agents, such as drug-like molecules and antibodies, are limited, posing challenges for molecular modeling investigations and the development of empirical scoring functions or machine learning predictors for this target. Furthermore, the reported entries in existing databases often contain major inconsistencies due to varied experiments and conditions, raising concerns about data quality. To address these issues, a pioneering database, HSADab, was established through an extensive review of >30,000 scientific publications published between 1987 and 2023. The database encompasses over 5000 affinity data points at multiple temperatures and >130 crystal structures, including both ligand-bound and apo forms. The current HSADab resource (www.hsadab.cn) serves as a reliable foundation for validating molecular simulation protocols, such as traditional virtual screening workflows using docking, end-point, and al-chemical free energy techniques. Additionally, it provides a valuable data source for the implementation of machine learning predictors, including plasma protein binding models and plasma protein-based drug design models.

Enhanced LSTM-based robotic agent for load forecasting in low-voltage distributed photovoltaic power distribution network.

To ensure the safe operation and dispatching control of a low-voltage distributed photovoltaic (PV) power distribution network (PDN), the load forecasting problem of the PDN is studied in this study. Based on deep learning technology, this paper proposes a robot-assisted load forecasting method for low-voltage distributed photovoltaic power distribution networks using enhanced long short-term memory (LSTM). This method employs the frequency domain decomposition (FDD) to obtain boundary points and incorporates a dense layer following the LSTM layer to better extract data features. The LSTM is used to predict low-frequency and high-frequency components separately, enabling the model to precisely capture the voltage variation patterns across different frequency components, thereby achieving high-precision voltage prediction. By verifying the historical operation data set of a low-voltage distributed PV-PDN in Guangdong Province, experimental results demonstrate that the proposed "FDD+LSTM" model outperforms both recurrent neural network and support vector machine models in terms of prediction accuracy on both time scales of 1 h and 4 h. Precisely forecast the voltage in different seasons and time scales, which has a certain value in promoting the development of the PDN and related technology industry chain.

Sleep promoting and omics exploration on probiotics fermented Gastrodia elata Blume.

Fermenting Chinese medicinal herbs could enhance their bioactivities. We hypothesized probiotic-fermented gastrodia elata Blume (GE) with better potential to alleviate insomnia than that of unfermented, thus the changes in chemical composition and the insomnia-alleviating effects and mechanisms of fermented GE on pentylenetetrazole (PTZ)-induced insomnia zebrafish were explored via high-performance liquid chromatography (HPLC) and mass spectroscopy-coupled HPLC (HPLC-MS), phenotypic, transcriptomic, and metabolomics analysis. The results demonstrated that probiotic fermented GE performed better than unfermented GE in increasing the content of chemical composition, reducing the displacement, average speed, and number of apoptotic cells in zebrafish with insomnia. Metabolomic investigation showed that the anti-insomnia effect was related to regulating the pathways of actin cytoskeleton and neuroactive ligand-receptor interactions. Transcriptomic and reverse transcription qPCR (RT-qPCR) analysis revealed that secondary fermentation liquid (SFL) significantly modulated the expression levels of neurod1, msh2, msh3, recql4, ercc5, rad5lc, and rev3l, which are mainly involved in neuron differentiation and DNA repair. Collectively, as a functional food, fermented GE possessed potential for insomnia alleviation.

Molecular Dynamics Simulation of the Rejuvenation Performance of Waste Cooking Oil with High Acid Value on Aged Asphalt.

Waste cooking oil's (WCO's) potential as a rejuvenator of aged asphalt has received attention in recent years, with the acid value of WCO affecting its rejuvenation effect. This study explored the rejuvenation effect of WCO with a high acid value on aged asphalt by using molecular dynamics simulation. First, the representative molecules of WCO with a high acid value and asphalt were determined. The rejuvenation effect of WCO on aged asphalt was analyzed by adding different contents of WCO to an aged asphalt model. The effect of WCO on the thermodynamic properties of the aged asphalt was analyzed. The results show that WCO can restore the thermodynamic properties of aged asphalt binder to a certain extent. Regarding the microstructure of rejuvenated asphalt, WCO molecules dispersed around asphaltenes weakened the latter's aggregation and improved the colloidal structure of the aged asphalt. In terms of interface adhesion properties, WCO can improve the adhesion properties between asphalt binder and SiO2, but it has limited influence on water sensitivity. The results allowed us to comprehensively evaluate the rejuvenation effect of WCO with a high acid value on aged asphalt and to explore its rejuvenation mechanism.

An efficient point cloud semantic segmentation network with multiscale super-patch transformer.

Efficient semantic segmentation of large-scale point cloud scenes is a fundamental and essential task for perception or understanding the surrounding 3d environments. However, due to the vast amount of point cloud data, it is always a challenging to train deep neural networks efficiently and also difficult to establish a unified model to represent different shapes effectively due to their variety and occlusions of scene objects. Taking scene super-patch as data representation and guided by its contextual information, we propose a novel multiscale super-patch transformer network (MSSPTNet) for point cloud segmentation, which consists of a multiscale super-patch local aggregation (MSSPLA) module and a super-patch transformer (SPT) module. Given large-scale point cloud data as input, a dynamic region-growing algorithm is first adopted to extract scene super-patches from the sampling points with consistent geometric features. Then, the MSSPLA module aggregates local features and their contextual information of adjacent super-patches at different scales. Owing to the self-attention mechanism, the SPT module exploits the similarity among scene super-patches in high-level feature space. By combining these two modules, our MSSPTNet can effectively learn both local and global features from the input point clouds. Finally, the interpolating upsampling and multi-layer perceptrons are exploited to generate semantic labels for the original point cloud data. Experimental results on the public S3DIS dataset demonstrate its efficiency of the proposed network for segmenting large-scale point cloud scenes, especially for those indoor scenes with a large number of repetitive structures, i.e., the network training of our MSSPTNet is much faster than other segmentation networks by a factor of tens to hundreds.

Chemopreventive effects of atractylenolide-III on mammary tumorigenesis via activation of the Nrf2/ARE pathway through autophagic degradation of Keap1.

The incidence of breast cancer is increasing annually, making it a major health threat for women. Chemoprevention using natural, dietary, or synthetic products has emerged as a promising approach to address this growing burden. Atractylenolide-III (AT-III), a sesquiterpenoid present in various medicinal herbs, has demonstrated potential therapeutic effects against several diseases, including tumors, nonalcoholic fatty liver disease, and cerebral ischemic injury. However, its impact on breast cancer chemoprevention remains unexplored. In this study, we used an N-methyl-N-nitrosourea (NMU)-induced rat breast cancer model and 17ß-estradiol (E2)-treated MCF-10A cells to evaluate the chemopreventive potential of AT-III on mammary tumorigenesis. AT-III inhibited mammary tumor progression, evidenced by reduced tumor volume and multiplicity, prolonged tumor latency, and the reversal of NMU-induced weight loss. Furthermore, AT-III suppressed NMU-induced inflammation and oxidative stress through the Nrf2/ARE pathway in breast cancer tissues. In vitro, AT-III effectively suppressed E2-induced anchorage-independent growth and cell migration in MCF-10A cells. Nrf2 knockdown attenuated the protective effects of AT-III, highlighting the pivotal role of Nrf2 in AT-III-mediated suppression of tumorigenesis. The mechanism involves the induction of Nrf2 expression by AT-III through the autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Overall, the results of this study indicate that AT-III is a promising candidate for breast cancer chemoprevention and provide valuable insights into its molecular interactions and signaling pathways.