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Abstract Background Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although intensive studies and therapeutic approaches, there are limited restorative treatments till now. Human embryonic stem cell (hESCs)-derived cortical neural progenitors have shown great potentials in ischemic stroke in adult brain. However, it is unclear whether they are feasible for cortical reconstruction in immature brain with hypoxic-ischemic encephalopathy. Methods By using embryonic body (EB) neural differentiation method combined with DAPT pre-treatment and quantitative cell transplantation, human cortical neuroblasts were obtained and transplanted into the cortex of hypoxic-ischemic injured brain with different dosages 2 weeks after surgery. Then, immunostaining, whole-cell patch clamp recordings and behavioral testing were applied to explore the graft survival and proliferation, fate commitment of cortical neuroblasts in vitro, neural circuit reconstruction and the therapeutic effects of cortical neuroblasts in HIE brain. Results Transplantation of human cortical neural progenitor cells (hCNPs) in HIE-injured cortex exhibited long-term graft overgrowth. DAPT pre-treatment successfully synchronized hCNPs from different developmental stages (day 17, day 21, day 28) to deep layer cortical neuroblasts which survived well in HIE injured brain and greatly prevented graft overgrowth after transplantation. Importantly, the cortical neuroblasts primarily differentiated into deep-layer cortical neurons and extended long axons to their projection targets, such as the cortex, striatum, thalamus, and internal capsule in both ipsilateral and contralateral HIE-injured brain. The transplanted cortical neurons established synapses with host cortical neurons and exhibited spontaneous excitatory or inhibitory post-synaptic currents (sEPSCs or sIPSCs) five months post-transplantation. Rotarod and open field tests showed greatly improved animal behavior by intra-cortex transplantation of deep layer cortical neuroblasts in HIE injured brain. Conclusions Transplanted hESCs derived cortical neuroblasts survive, project to endogenous targets, and integrate into host cortical neural circuits to rescue animal behavior in the HIE-injured brain without graft overgrowth, providing a novel and safe cell replacement strategy for the future treatment of HIE.

Abstract Background To investigate the role of lncRNA LINC00665 in modulating ovarian cancer stemness and its influence on treatment resistance and cancer development. Methods We isolated ovarian cancer stem cells (OCSCs) from the COC1 cell line using a combination of chemotherapeutic agents and growth factors, and verified their stemness through western blotting and immunofluorescence for stem cell markers. Employing bioinformatics, we identified lncRNAs associated with ovarian cancer, with a focus on LINC00665 and its interaction with the CNBP mRNA. In situ hybridization, immunohistochemistry, and qPCR were utilized to examine their expression and localization, alongside functional assays to determine the effects of LINC00665 on CNBP. Results LINC00665 employs its Alu elements to interact with the 3’-UTR of CNBP mRNA, targeting it for degradation. This molecular crosstalk enhances stemness by promoting the STAU1-mediated decay of CNBP mRNA, thereby modulating the Wnt and Notch signaling cascades that are pivotal for maintaining CSC characteristics and driving tumor progression. These mechanistic insights were corroborated by a series of in vitro assays and validated in vivo using tumor xenograft models. Furthermore, we established a positive correlation between elevated CNBP levels and increased disease-free survival in patients with ovarian cancer, underscoring the prognostic value of CNBP in this context. Conclusions lncRNA LINC00665 enhances stemness in ovarian cancer by mediating the degradation of CNBP mRNA, thereby identifying LINC00665 as a potential therapeutic target to counteract drug resistance and tumor recurrence associated with CSCs.

Abstract Coiled-coil domain containing 88C (CCDC88C) is a component of non-canonical Wnt signaling, and its dysregulation causes colorectal cancer metastasis. Dysregulated expression of CCDC88C was observed in lymph node metastatic tumor tissues of breast cancer. However, the role of CCDC88C in breast cancer metastasis remains unclear. To address this, the stable BT549 and SKBR3 cell lines with CCDC88C overexpression or knockdown were developed. Loss/gain-of-function experiments suggested that CCDC88C drove breast cancer cell motility in vitro and lung and liver metastasis in vivo. We found that CCDC88C led to c-JUN-induced transcription activation. Overlapping genes were identified from the genes modulated by CCDC88C and c-JUN. CEMIP, one of these overlapping genes, has been confirmed to confer breast cancer metastasis. We found that CCDC88C regulated CEMIP mRNA levels via c-JUN and it exerted pro-metastatic capabilities in a CEMIP-dependent manner. Moreover, we identified the CCDC88C as a substrate of polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6). GALNT6 was positively correlated with CCDC88C protein abundance in the normal breast and breast cancer tissues, indicating that GALNT6 might be associated with expression patterns of CCDC88C in breast cancer. Our data demonstrated that GALNT6 maintained CCDC88C stability by promoting its O-linked glycosylation, and the modification was critical for the pro-metastatic potential of CCDC88C. CCDC88C also could mediate the pro-metastatic potential of GALNT6 in breast cancer. Collectively, our findings uncover that CCDC88C may increase the risk of breast cancer metastasis and elucidate the underlying molecular mechanisms.

IntroductionThe rapid advancement of digital technology has catalyzed the emergence of “digital villages,” presenting both new opportunities and challenges for the digital transformation of agriculture. This transformation has become a core driving force behind sustainable agricultural development. This paper utilizes panel data from 30 provincial-level administrative regions of mainland China (excluding Tibet) for the period 2011 to 2020 to explore how digital rural development (DRD) impacts agricultural green total factor productivity (AGTFP) and examines its underlying mechanisms.MethodsRegarding variable measurement, the study employs the entropy weighting method to quantify the DRD and uses an extended Data Envelopment Analysis-Malmquist model to assess AGTFP. For the research approach, the study constructs a two-way fixed effects model to evaluate the impact of DRD on AGTFP and explores the underlying mechanisms. Specifically, the study conducts benchmark regression analysis, endogeneity tests, robustness tests, mechanism examinations, and heterogeneity tests.Results(1) DRD significantly enhances AGTFP, a conclusion that remains robust following the province-year clustering robust standard error estimates, winsorization tests, and excluding COVID-19-affected years. (2) Mechanistic analysis indicates that DRD primarily boosts AGTFP by promoting the development of digital inclusive finance (DIF) and facilitating the integration of primary, secondary, and tertiary industries (IPST). (3) Heterogeneity tests show that the positive impact of DRD on AGTFP is more pronounced in regions with higher levels of informatization and central regions of China.DiscussionTo harness DRD’s potential more effectively in fostering sustainable agricultural development, policymakers should concentrate on DIF and the IPST. Additionally, the government should pay close attention to disparities in informatization levels and resource allocation across regions and develop targeted strategies accordingly. Fundamentally, this study aims to elucidate China’s efficacy in rural digitalization and the green transformation of agriculture to an international audience. It seeks to provide insights and guidance on formulating more scientific, efficient, and sustainable strategies for agricultural development worldwide, thereby promoting green agricultural growth and supporting rural revitalization.

The study analyzed hourly extreme precipitation events in Chongqing and its six sub-regions from 2011 to 2021 during the warm season. Results showed uneven distribution of the 99.7th percentile hourly extreme precipitation threshold, with lower thresholds along the Yangtze River valley and higher thresholds in the Daba Mountains and Wuling Mountains. Both hourly extreme precipitation amount (HEPA) and intensity (HEPI) exhibited higher values in surrounding areas and lower values in the center, with the western, northeast, and southeastern regions experiencing the highest values. Spatial distribution of hourly extreme precipitation frequency varied, with higher frequencies in the northwestern and southern parts of Chongqing. Interannually, hourly extreme precipitation amount slightly increased, while intensity fluctuated. Monthly peak values for amount, frequency, and intensity occurred in July or August, and on a daily scale, the periods from 03:00 to 07:00 and 17:00 to 21: 00 exhibited higher values for amount and frequency, while the period from 11 :00 to 16:00 showed lower values. In summary, the study provided insights into the spatial and temporal patterns of hourly extreme precipitation events in Chongqing and its sub-regions during the warm season, highlighting variations in thresholds, distribution, and trends over the studied period.

Abstract Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

The anatomical structure of the medulla oblongata is complex, its nerve fibers are dense, and its blood vessels are complex. Clinical manifestations of ischemic damage to the medulla oblongata are therefore relatively diverse, and include vertigo, dysphagia, and dysarthria. Although facial paralysis may also occur, medullary infarction with facial paralysis as the first and only symptom is rare. Herein, we report a case of medullary infarction with ipsilateral central facial paralysis as the only symptom.

Purpose: This study explored whether a free-breathing mean heart dose (FB-MHD) of 4 Gy is a reliable dose threshold for selecting left breast cancer patients after modified radical mastectomy suitable for deep inspiration breath-hold (DIBH) and developed anatomical indicators to predict FB-MHD for rapid selection. Materials and methods: Twenty-three patients with left breast cancer treated with DIBH were included to compare FB and DIBH plans. The patients were divided into the high-risk (FB-MHD ≥ 4 Gy) and low-risk (FB-MHD

Females and males are known to be different in the prevalences of multiple psychiatric disorders, while the underlying neural mechanisms are unclear. Based on non-invasive neuroimaging techniques and graph theory, many researchers have tried to use a small-world network model to elucidate sex differences in the brain. This manuscript aims to compile the related research findings from the past few years and summarize the sex differences in human brain networks in both normal and psychiatric populations from the perspective of small-world properties. We reviewed published reports examining altered small-world properties in both the functional and structural brain networks between males and females. Based on four patterns of altered small-world properties proposed: randomization, regularization, stronger small-worldization, and weaker small-worldization, we found that current results point to a significant trend toward more regularization in normal females and more randomization in normal males in functional brain networks. On the other hand, there seems to be no consensus to date on the sex differences in small-world properties of the structural brain networks in normal populations. Nevertheless, we noticed that the sample sizes in many published studies are small, and future studies with larger samples are warranted to obtain more reliable results. Moreover, the number of related studies conducted in psychiatric populations is still limited and more investigations might be needed. We anticipate that these conclusions will contribute to a deeper understanding of the sex differences in the brain, which may be also valuable for developing new methods in the treatment of psychiatric disorders.

Abstract It is urgent to develop low-reflection electromagnetic interference shielding material to shield electromagnetic waves (EMW) and reduce their secondary radiation pollution. Herein, an electromagnetic interference shielding nanofiber film is composed of ZnO and carbon nanofiber (CNF) via electrospinning and carbonization approachs, and subsequently coating perfuorooctyltriethoxysilane as a protective layer. On the one hand, ZnO coated by porous carbon, which is derived from ZIF-8, endows the nanofiber film low reflection property through optimizing impedance matching between free space and the nanofiber film. On the other hand, the nanofiber film possesses high electromagnetic interference shielding efficiency, which is beneficial by excellent electrical conductivity of CNF derived from waste leather scraps. Furthermore, the nanofiber film involves abundant interface, which contributes to high interfacial polarization loss. Thus, the nanofiber film with a thickness of 250 μm has electrical conductivity of 53 S/m and shielding efficiency of 50 dB. The reflection coefficient of the nanofiber film is inferior to 0.4 indicates that most of EMW are absorbed inside the materials and the nanofiber film is effective in reducing secondary radiation contamination of electromagnetic waves. Fortunately, the nanofiber film exhibits outstanding solar harvesting performance (106 ℃ at 1 sun density) and good self-cleaning performance, which ensure that the nanofiber film can work in harsh environments. This work supplies a credible reference for fabricating low-reflection electromagnetic shielding nanofiber film to reduce secondary radiation pollution and facilitates the upcycling of waste leather scraps. Graphic abstract

Matching planetary remote sensing images (PRSI) is essential for deep space exploration. Through matching optical images collected by different probes, the terrain of planets can be accurately mapped; however, PRSI lacks surface texture information and exhibits noticeable nonlinear radiation differences, e.g., illumination differences. It is not easy to achieve satisfactory results through traditional matching methods. In order to cope with the above problems, a new PRSI matching method has been proposed. It can extract low–high frequency features by building double-frequency scale space. In addition, we also use the nonmaximum suppression strategy for rejecting overlapped feature points, which reduces the time consumption and improves the matching accuracy. The experimental results show that the proposed method can effectively match PRSI and be superior to comparable methods.

[INLINE:1] Vascular etiology is the second most prevalent cause of cognitive impairment globally. Endothelin-1, which is produced and secreted by endothelial cells and astrocytes, is implicated in the pathogenesis of stroke. However, the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood. Here, using mice in which astrocytic endothelin-1 was overexpressed, we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia (1 hour of ischemia; 7 days, 28 days, or 3 months of reperfusion). We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion. Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6, which were differentially expressed in the brain, were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke. Moreover, the levels of the enriched differentially expressed proteins were closely related to lipid metabolism, as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis. Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine, sphingomyelin, and phosphatidic acid. Overall, this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Lignin is one of the building blocks of plant cell walls, and the study of the spectral characterization of its cleavage process can help to monitor the production and reuse of straw after decay. In this paper, four theoretical model structures of lignin formed by lignin G monomers and connected by β-O-4 bonding type were optimized and calculated based on the density functional theory using the B3LYP/3-21g and B3LYP/6-311g basis sets. The results showed that the theoretical infrared spectra of lignin increased sequentially in the absorption peaks of 1500 cm−1 blue shift and 2932 cm−1 and 1200 cm−1 red shift, while the latter three theoretical models showed new infrared absorption peaks of 716 cm−1 and 823 cm−1 due to the presence of the β-O-4 structure, which is of great value for the theoretical spectral study of organic macromolecules and also provides data support for the spectral change in lignin in the degradation of graminaceous plants.

The storage time of rice determines its quality and nutritional value, and the longer the storage time, the greater the impact. In this study, different excitation wavelengths (405 nm, 365 nm, 310 nm) were used to detect the fluorescence spectrum of “Dongdao 12” brown rice. Support vector machine (SVM), K-nearest neighbor (KNN), and wide neural network (WNN) were used for modeling and analysis. Under the excitation of 310 nm, the accuracy of WNN classification is up to 99.2%. In order to reduce the scattering effect and other interference in the data, multiplicative scatter correction (MSC), standard normal variable (SNV), and Savitzky–Goray smoothing (SG) preprocessing methods were used. The results showed that SG + KNN classification achieved an accuracy of 99.3% under 310 nm excitation. In order to further improve the classification accuracy, the original spectrum and the preprocessed spectrum under different excitation light sources were fused. The classification accuracy of all methods was improved, and the original data fusion was combined with the WNN model to reach 100%. It shows that fluorescence spectroscopy has excellent potential in identifying rice storage years.

The origin of agricultural products significantly influences their quality and safety. Fluorescence spectroscopy was used to analyse Japonica rice 830, grown in different areas of Jilin Province, by examining rice seed, brown rice, and rice flour from 12 origins. Fluorescence spectra were pre-processed through normalisation and smoothing to remove noise. These processed spectra were input into decision trees, support vector machines (SVMs), K-nearest neighbour (KNN), and neural network models for classification. The analysis revealed that the combined four models achieved an average classification accuracy of 98.05% with a computation time of 180 s, while the reduced-scale models improved accuracy to 98.36% and reduced computation time to 11.25 s. Additionally, prediction models using standard rice starch content values across different states achieved R² values over 0.8. This method provides a rapid, precise approach for assessing rice quality and origin, demonstrating significant potential for application in rice analysis.

Reducing traffic energy consumption is crucial for smart cities, and vehicle carbon emissions are a key energy indicator. Traffic signal control (TSC) is a useful method because it can affect the energy consumption of vehicles on the road by controlling the stop-and-go of vehicles at traffic intersections. However, setting traffic signals to reduce energy consumption will affect traffic efficiency and this is not in line with traffic management objectives. Current studies adopt multi-objective optimization methods with high traffic efficiency and low carbon emissions to solve this problem. However, most methods use static weights, which cannot adapt to complex and dynamic traffic states, resulting in non-optimal performance. Current energy indicators for urban transportation often fail to consider passenger fairness. This fairness is significant because the purpose of urban transportation is to serve people’s mobility needs not vehicles. Therefore, this paper proposes Multi-objective Adaptive Meta-DQN TSC (MMD-TSC), which introduces a dynamic weight adaptation mechanism to simultaneously optimize traffic efficiency and energy saving, and incorporates the per capita carbon emissions as the energy indicator. Firstly, this paper integrates traffic state data such as vehicle positions, velocities, vehicle types, and the number of passengers and incorporates fairness into the energy indicators, using per capita carbon emissions as the target for reducing energy consumption. Then, it proposes MMD-TSC with dynamic weights between energy consumption and traffic efficiency as reward functions. The MMD-TSC model includes two agents, the TSC agent and the weight agent, which are responsible for traffic signal adjustment and weight calculation, respectively. The weights are calculated by a function of traffic states. Finally, the paper describes the design of the MMD-TSC model learning algorithm and uses a SUMO (Simulation of Urban Mobility) v.1.20.0 for traffic simulation. The results show that in non-highly congested traffic states, the MMD-TSC model has higher traffic efficiency and lower energy consumption compared to static multi-objective TSC models and single-objective TSC models, and can adaptively achieve traffic management objectives. Compared with using vehicle average carbon emissions as the energy consumption indicator, using per capita carbon emissions achieves Pareto improvements in traffic efficiency and energy consumption indicators. The energy utilization efficiency of the MMD-TSC model is improved by 35% compared to the fixed-time TSC.

Abstract The development of functional textiles combining conventional apparel with advanced technologies for personal health management (PHM) has garnered widespread attention. However, the current PHM textiles often achieve multifunctionality by stacking functional modules, leading to poor durability and scalability. Herein, a scalable and robust PHM textile is designed by integrating electrical, radiative, and solar heating, electromagnetic interference (EMI) shielding, and piezoresistive sensing performance onto cotton fabric. This is achieved through an uncomplicated screen‐printing process using silver paste. The conductivity of the PHM textile is ≈1.6 × 104 S m−1, ensuring an electric heating temperature of ≈134 °C with a low voltage of 1.7 V, as well as an EMI shielding effectiveness of ≈56 dB, and human motion monitoring performance. Surprisingly, the radiative/solar heating capability of the PHM textile surpasses that of traditional warm leather. Even after undergoing rigorous physical and chemical treatments, the PHM textile maintains terrific durability. Additionally, the PHM textile possesses maneuverable scalability and comfortable wearability. This innovative work opens up new avenues for the strategic design of PHM textiles and provides an advantageous guarantee of mass production.

Chirality, a fundamental design feature at all levels of life organization, has shown great capability in guiding cell‐fate determination and tissue regeneration. Chirality‐directed differentiation programs involve remarkable changes in transcriptional networks, yet whether epigenetic regulatory events are also required is less well understood. Herein, by combining high‐throughput m6A MeRIP sequencing, RIP‐qPCR, and gene modulation techniques, it is demonstrated that biomimetic chiral nanofibrils can bidirectionally regulate wilms tumor 1 associated protein (WTAP)‐mediated m6A RNA methylation to guide macrophages polarization for tissue regeneration. The biomimic chiral nanofibril hydrogels are fabricated using a self‐assembly approach based on C2‐symmetric phenylalanine derivatives. In vitro and in vivo studies indicated that the L‐nanofibrils exhibit a greater propensity to promote M2‐macrophage polarization than D‐nanofibrils, thereby favoring osteogenesis. Then, m6A‐MeRIP sequencing revealed a unique chirality‐dependent m6A methylation level in macrophages, which was gated by a competitive pair of CCM3‐FAK through enantioselectively integrin recognition. L‐nanofibrils considerably suppressed WTAP‐mediated m6A methylation by promoting Itgα3‐FAK expression and paxillin‐driven mechanotransduction, whereas D‐nanofibrils induced WTAP‐mediated m6A methylation by favoring ItgαV‐CCM3 expression and suppressing mechanotransduction. Furthermore, the gain‐of‐function and loss‐of‐function experiments and RIP‐qPCR demonstrate that the WTAP expression could direct macrophage polarization via manipulating the functional molecule B7‐H3 (CD276). Thus, a mechano‐epigenetic mechanism of chirality‐mediated cell‐fate determination is unveiled, which holds remarkable promise in the realm of assisted regenerative material design.

Abstract Long noncoding RNAs (lncRNAs) play important roles in regulating HIV-1 infection and virus-host interactions. However, it is unclear whether and how ART alters lncRNAs in HIV-infected patients. In the present study, we investigated changes of lncRNAs in PBMCs from HIV-1 patients pre- and post-ART. We identified a total of 974 lncRNAs whose expression was restored to normal levels after ART. Cis-acting analysis showed that six lncRNAs have cis-regulated target genes, among which RP11-290F5.1 and interferon regulatory factor 2 (IRF2) were reported to promote HIV replication. Furthermore, we found that lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression in PBMCs from HIV-1 infected patients after ART, was significantly upregulated by RNA-seq and qRT-PCR assays. KEGG analysis of CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway and pathways related to cell cycle and DNA replication. Our findings thus reveal the dynamic change of lncRNAs in people living with HIV-1 pre- and post-ART and warrant further investigation of the role of lncRNAs in HIV-1 pathogenesis and treatment.

BackgroundInvestigations assessing the value of metagenomic next-generation sequencing (mNGS) for distinguish Aspergillus infection from colonization are currently insufficient.MethodsThe performance of mNGS in distinguishing Aspergillus infection from colonization, along with the differences in patients’ characteristics, antibiotic adjustment, and lung microbiota, were analyzed.ResultsThe abundance of Aspergillus significantly differed between patients with Aspergillus infection (n=36) and colonization (n=32) (P < 0.0001). Receiver operating characteristic (ROC) curve result for bronchoalveolar lavage fluid (BALF) mNGS indicated an area under the curve of 0.894 (95%CI: 0.811-0.976), with an optimal threshold value of 23 for discriminating between Aspergillus infection and colonization. The infection group exhibited a higher proportion of antibiotic adjustments in comparison to the colonization group (50% vs. 12.5%, P = 0.001), with antibiotic escalation being more dominant. Age, length of hospital stay, hemoglobin, cough and chest distress were significantly positively correlated with Aspergillus infection. The abundance of A. fumigatus and Epstein-Barr virus (EBV) significantly increased in the infection group, whereas the colonization group exhibited higher abundance of A. niger.ConclusionBALF mNGS is a valuable tool for differentiating between colonization and infection of Aspergillus. Variations in patients’ age, length of hospital stay, hemoglobin, cough and chest distress are observable between patients with Aspergillus infection and colonization.

Objective: To compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and surgery in treating vaginal high-grade squamous intraepithelial lesions (HSIL) after hysterectomy due to cervical cancer (CC) or precancerous lesions. Methods: A retrospective study was performed comprising 41 women with histologically confirmed vaginal HSIL after hysterectomy for CC or cervical HSIL. Patients were treated with surgery or ALA-PDT and were followed up at 3, 6 and 12 months and then every six months afterwards. Clinical data were collected and the efficacy and safety of the two groups were analyzed. Results: Of the 41 patients with vaginal HSIL after hysterectomy, 18 were treated with ALA-PDT and 23 underwent surgery. There was no significant difference in the lesions’ complete remission (CR) rate or the human papillomavirus (HPV) clearance rate between the ALA-PDT group and the surgery group (P > 0.05). In the surgery group, the clearance rate of HPV16/18 was higher than that of other high-risk HPV (HR-HPV) and HPV16/18 combined with other HR-HPV (87.50 % vs. 45.45 % vs. 0.00 %, P = 0.014). No significant difference in the recurrence rate between the two groups was noted (P > 0.05). And none of the patients progressed. In the surgery group, one patient developed significant thickening of the vaginal stump, and one patient had increased vaginal discharge. In women treated with ALA-PDT, there was no vaginal bleeding or harmful effects on the organizational structure or functions compared to the surgery group. Conclusions: The efficacy of ALA-PDT was comparable to that of surgery in treating vaginal HSIL following hysterectomy due to CC or cervical HSIL, with fewer side effects.

Background Cadmium (Cd) is hazardous to human health because of its cytotoxicity and long biological half-life. Azoramide is a small molecular agent that targets the endoplasmic reticulum (ER) and moderates the unfolded protein response. However, its role in Cd-induced cytotoxicity remains unclear. This study was performed to investigate the protective effect of azoramide against Cd-induced cytotoxicity and elucidate its underlying mechanisms. Methods Inductively coupled plasma‒mass spectrometry was used to measure Cd concentrations in each tissue of ICR male mice. The human proximal tubule epithelial cell line HK-2 and the human retinal pigment epithelial cell line ARPE-19 were used in the in vitro study. Cell apoptosis was determined by DAPI staining, JC-1 staining, and annexin V/propidium iodide double staining. Intracellular oxidative stress was detected by MitoSOX red staining, western blot, and quantitative real-time PCR. Moreover, ER stress signaling, MAPK cascades, and autophagy signaling were analyzed by western blot. Results The present data showed that Cd accumulated in various organs of ICR mice, and the concentrations of Cd in the studied organs, from high to low, were as follows: liver > kidney > testis > lung > spleen > eye. Our study demonstrated that azoramide inhibited ER stress by promoting BiP expression and suppressing the PERK-eIF2α-CHOP pathway. Additionally, we also found that azoramide significantly decreased ER stress-associated radical oxidative species production, attenuated p38 MAPK and JNK signaling, and inhibited autophagy, thus suppressing apoptosis in HK-2 and ARPE-19 cells. Conclusion Our study investigated the effect of azoramide on Cd-induced cytotoxicity and revealed that azoramide may be a therapeutic drug for Cd poisoning.

Background and objective Since the popularization of computed tomography (CT) technology, the detection rate of pulmonary ground glass nodules (GGNs) with imaging follow-up as the main management method has increased significantly. The purpose of this study is to quantitatively analyze the changes of pulmonary GGNs during the follow-up process with three-dimensional reconstruction technology, explore the natural progression of pulmonary GGNs, and provide effective basis for clinical guidance for patients to conduct reasonable management of nodules. Methods A total of 115 cases of pulmonary GGNs with regular follow-up in the Combined Outpatient Department of Zhoushan Hospital from March 2015 to November 2022 were enrolled. Quantitative imaging features of nodules were extracted by semi-automatic segmentation of 3D Slicer software to evaluate the growth of nodules and clinical intervention during follow-up. Results The average baseline age of the patients was (56.9±10.1) yr. The mean follow-up time was (48.8±18.9) months. The two-dimensional diameter of baseline CT scan was (7.9±2.9) mm, and the maximum three-dimensional diameter was (10.1±3.4) mm. The two-dimensional diameter of the last CT scan was (9.9±4.7) mm, and the maximum three-dimensional diameter was (11.4±5.1) mm. A total of 27 cases (23.5%) showed an increase during follow-up, with a median volume doubling time of 822 days and a median mass doubling time of 1,007 days. 32 cases were surgically resected, including 6 cases of invasive adenocarcinoma (IAC), 16 cases of minimally invasive adenocarcinoma (MIA), 8 cases of adenocarcinoma in situ (AIS) and 2 cases of atypical adenomatous hyperplasia (AAH). Five nodules underwent surgical intervention due to the progression of two-dimensional diameter, which was pathologically confirmed as pre-invasive lesions, but their three-dimensional maximum diameter showed no significant change. Nodular morphology, lobulated sign, spiculated sign and vacuole signs all promoted the growth of nodules in univariate analysis. There were significant differences in age, baseline diameter, mean CT value, median CT value, 10% and 90% percentile CT number between the growth group and the stable group (P

Abstract Sepsis is a severe organ dysfunction typically caused by wound infection which leads to septic shock, organ failure or even death if no early diagnosis and property medical treatment were taken. Herein, we report a soft, wearable and battery‐free wound dressing system (WDS) for wireless and real‐time monitoring of wound condition and sepsis‐related biomarker (procalcitonin [PCT]) in wound exudate for early sepsis detection. The battery‐free WDS powered by near‐field communication enables wireless data transmission, signal processing and power supply, which allows portable intelligent wound caring. The exudate collection associates with soft silicone based microfluidic technologies (exudate collection time within 15 s), that can filtrate contamination at the cell level and enable a superior filtration rate up to 95% with adopting microsphere structures. The battery‐free WDS also includes state‐of‐the‐art biosensors, which can accurate detect the pH value, wound temperature, and PCT level and thus for sepsis diagnosis. In vivo studies of SD rats prove the capability of the WDS for continuously monitoring wound condition and PCT concentration in the exudate. As a result, the reported fully integrated WDS provides a potential solution for further developing wearable, multifunctional and on‐site disease diagnosis.

Torrential rain with the greatest social impact in Chongqing in the year of 2021 occurred in the central and eastern parts of Sichuan basin from August 7 to August 8. Using multi-source observation and ERA5 reanalysis data, the characteristics of mesoscale convective systems during the heavy rain process were analyzed. The heavy rainfall occurred under the background of the warm Southwest Vortex induced by the trough moving into the Sichuan basin, and had evident characteristics of stages, bounds, and extremes. The heavy rainfall formed successively in the southeast of the Southwest Vortex center and near the boundary layer convergence line in the east and south of the Southwest Vortex. The heavy rainfall of each stage was produced by mesoscale-β convective systems which moved slowly and maintained for 3~6 h. Warm and humid instability and weak vertical wind shear provided favorable environment for the development of mesoscale convective systems. Vorticity analysis showed that the development of the Southwest Vortex was mainly due to the low-level convergence and vertical vorticity transport. However, the development of positive vorticity in the rainstorm area was not exactly the same as that of the Southwest Vortex, and the horizontal vorticity tilting effect was relatively significant. The positive vorticity of the heavy rainstorm area in the first stage was mainly due to the significant low-level convergence, vertical vorticity transport, and horizontal vorticity tilting effect near the Southwest Vortex center in the middle and low level troposphere. The positive vorticity of the heavy rainstorm area in the second and third stages were mainly due to the horizontal vorticity tilting effect above the boundary layer and the convergence in the boundary layer. The boundary convergence triggered mesoscale convective activities in the warm and humid atmosphere, which promoted the heavy rain in the second and the third stages.

Nowadays, data analysis is been the most important means to realize power scheduling in smart grids. However, the sharp increase in business data of grids has posed great challenges for this purpose. To deal with such issue, this paper utilizes deep learning to discover hidden rules from massive large-scale big data and particle swarm optimization (PSO) algorithm for generation of control decision. Therefore, an intelligent scheduling control method for smart grid based on deep learning is proposed in this paper. By modeling the historical data of the power company, the long short-term memory algorithm can effectively extract the effective features and realize the prediction of the coal consumption of the unit under certain conditions. At the same time, a kind of intelligent power scheduling algorithm is designed by using PSO, so as to save energy and reduce emissions as much as possible while fulfilling the real-time power generation task. Experiments on a real-world smart grid dataset show that the proposal can achieve a relatively good performance with respect to intelligent scheduling.

Abstract Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent autoimmune encephalitis and is closely related to catatonia. This study aimed to investigate the clinical features and disease outcomes of adult catatonic anti-NMDAR encephalitis patients. Methods Adult patients diagnosed with anti-NMDAR encephalitis between January 2013 and October 2021 were retrospectively enrolled in this study. According to the Bush Francis Catatonia screening instrument (BFCSI), patients were divided into two groups: those with catatonia and those without catatonia. The modified Rankin scale (mRS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), Neuropsychiatric Inventory (NPI), Patient Health Questionnaire-9 (PHQ-9) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7) scores were assessed at follow-up. The Mann–Whitney U test (nonparametric), Student’s t test (parametric), and chi-squared test were used to analyse the differences between the two groups. Results Eighty-four patients were recruited, including twenty-five catatonic patients and fifty-nine noncatatonic patients. Among them, 28 had positive antibody only in cerebrospinal fluid (CSF), 4 had positive antibody only in serum and 52 had positive antibody both in CSF and serum. Catatonic patients experienced more disturbance of consciousness (p = 0.01), aggression (p = 0.046) and affective disorders (p = 0.043) than noncatatonic patients. The mRS scores of the catatonia group assessed at admission (p = 0.045) were worse than those of the non-catatonia group. Catatonic patients were more inclined to develop deep vein thrombosis (p = 0.003), decubitus (p = 0.046), pneumonia (p = 0.025), and to be admitted to the intensive care unit (ICU) (p = 0.011) than noncatatonic patients. All patients in the catatonia group received first-line immunotherapy. At the 24-month follow-up, 2 patients in the catatonia group did not achieve good outcomes. At the last follow-up, the catatonia group had more relapses (p = 0.014) and more neuropsychiatric problems (p = 0.035). Conclusions Adult anti-NMDAR encephalitis patients with catatonia present distinct clinical features in disease course and are prone to experience more relapses and long-term neuropsychiatric problems than those without catatonia.

Abstract Brachial plexus root avulsion (BPRA) is frequently caused by high-energy trauma including traffic accident and birth trauma, which will induces massive motoneurons (MNs) death as well as loss of motor and sensory function in the upper limb. The death of MNs is attributed to energy deficiency, neuroinflammation and oxidative stress at the injured ventral horn of spinal cord triggered by BPRA injury. It has been reported which aldose reductase (AR), an endogenous enzyme that catalyzes fructose synthesis, positively correlates with the poor prognosis following cerebral ischemic injury, diabetic retinopathy and diabetic peripheral neuropathy. However, the role of AR in BPRA remains unknown. Herein, we used a mouse model and found that in the spinal cord of BPRA mice, the upregulation of AR correlated significantly with (1) an inactivated SIRT1–AMPK–mTOR pathway and disrupted autophagy; (2) increased byproducts accumulation of lipid peroxidation metabolism and neuroinflammation; and (3) increased MNs death. Furthermore, our results demonstrated the role of AR in BPRA injury whereby the absence of AR (AR knockout mice, AR−/−) prevented the hyper-neuroinflammation and disrupted autophagy as well as motor neuron death caused by BPRA injury. Finally, we further demonstrate that AR inhibitor epalrestat is neuroprotective against BPRA injury by increasing autophagy level, alleviating neuroinflammation and rescuing MNs death in mice. Collectively, our data demonstrate that the AR upregulation in the spinal cord is an important factor contributing to autophagy disruption, neuroinflammation and MNs death following brachial plexus roots avulsion in mice. Our study also provides a promising therapy drug to assist re-implantation surgery for the treatment of BPRA.

Clear cell adenocarcinoma of the cervix (CCAC) is a special type of HPV-independent cervical cancer. It has a low incidence rate, can be difficult to diagnose early, has a poor prognosis. Its peak incidence is in adolescence, which poses a great threat to women’s health. Therefore, it is very important to explore the pathogenesis of cervical clear cell adenocarcinoma to guide subsequent treatment and prevention. This study analyzed 3 juvenile patients with CCAC diagnosed at the First Affiliated Hospital of Zhengzhou University. Using next-generation sequencing methods, we analyzed the pathogenesis of the patients and their close relatives by analyzing the genetic alterations of patients. CMTM5 was identified as the only shared mutated gene. Using published literature and comparative analyses of related disease-causing genes, 6 of the 19 genes (ALKBH7, MYCBP, MZF1, RNF207, RRS1, and TUSC2) were screened as genes with mutations in patients and had higher mutation rates in reproductive cancers. Pathway analysis showed that downregulated genes in non-HPV cervical cancer were mainly related to the immune system response, suggesting that non-HPV cervical cancer differs from HPV-infected cervical cancer in that the immune response is weaker, which is consistent with the weak correlation with viral infection.

Abstract For bone defect repair, it is critical to utilize biomaterials with pro‐angiogenic properties to enhance osteogenesis. Hydroxyapatite (HA)‐based materials widely used in clinical applications have shown much potential for bone repair. However, their predominant calcium phosphate (CaP) composition and poor biodegradability limit their angiogenic potential and hence osteogenic efficiency of HA‐based materials. Here, a magnesium ion‐doped calcium silicate/HA composite microscaffold (Mg‐CS/HA) is fabricated to enhance angiogenesis and osteogenic efficiency for bone repair. Incorporation of CS improved the biodegradability of the Mg‐CS/HA microscaffold, which could simultaneously release Si and Mg bioactive ions during the early stage of implantation, synergistically enhancing angiogenesis and osteogenic efficiency. In co‐culture systems, the synergistic effects of Si and Mg ions promote the “osteogenesis‐angiogenesis coupling effect.” In vivo, the Mg‐CS/HA microscaffold could significantly promote reconstruction of the vascular network and bone regeneration. This study thus provides a new strategy for coordinated release of bioactive ions to achieve synergistic effects on vascularized bone regeneration by HA‐based bone implant materials.

Abstract Early diagnosis can effectively improve the survival of glioblastoma multiforme (GBM). A specific imaging technique that is simultaneously deep penetrating and sensitive to small tissue changes is desired to identify GBM. Due to its excellent features in signal contrast, detection sensitivity, and none or little attenuation in tissue, magnetic particle imaging (MPI) possesses great potential in cancer diagnosis, especially when the imaging modality is equipped with specifically targeted nanoprobes. However, when gliomas are small, the blood–brain barrier (BBB) is complete and prevents nanoprobes from entering the brain, which negates the theranostic effect. This study proposes a biomimetic nanoplatform that assist the MPI tracers in breaking through the BBB and then demonstrate a targeted and sensitive diagnosis of GBM. Afterward, the photothermal therapy and immune regulation show an excellent therapeutic effect on the GBM. It is experimentally confirmed that the MPI signal does not decay with tissue depth and shows excellent sensitivity for thousands‐cells. Only small animals are conducted in this study due to the limitations of the current commercial MPI scanner, however, this research theoretically enables large animal and human studies, which encourages a promising pathway toward the noninvasive diagnosis of early‐stage GBM in clinics.

Recent studies have indicated that the invasive apple snail (Pomacea canaliculata) exhibits tolerance to the salinity levels present in coastal agricultural soils, suggesting that apple snails could potentially invade salt-affected coastal agricultural areas. However, the effects of the alien snail Pomacea canaliculata invasion on coastal saline soils, such as in terms of soil properties, microbial diversity, and abundance, remain poorly understood. To fill this gap, we conducted experiments involving three salinity levels (0, 2‰, and 5‰, w/w), coupled with varying snail densities (0, 5, and 10 snails per box), applied to agricultural soil. We analyzed soil chemical properties, enzyme activities, and bacterial communities. The findings revealed that heightened soil salinity increased soil electrical conductivity (EC) (exceeding 1312.67 μS cm−1). Under saline conditions, snail treatments significantly increased the soil organic matter (SOM) content from 15.82 mg kg−1 to 18.69 mg kg−1, and concurrently diminished the dissolved organic carbon (DOC) from 47.45 mg kg−1 to 34.60 mg kg−1. Both snail and salinity treatments resulted in ammonia nitrogen (NH4+-N) accumulation, while nitrate nitrogen (NO3−-N) concentrations remained low in salt-affected soils. A notable positive correlation existed between the EC and the activities of hydroxylamine reductase (HR) and peroxidase (POD), where HR exhibited a positive correlation with NH4+-N, and POD displayed a negative correlation with NO3−-N. Salinity substantially decreased the diversity and altered the composition of soil bacterial community, with the phyla Bacteroidota, Proteobacteria, and Firmicutes adapting to salt-affected soil environment and proliferating. Structural equation modeling (SEM) analysis indicated that snails exerted a direct influence on soil-available nitrogen (including NO3−-N and NH4+-N), while salinity impacted available nitrogen by modulating soil enzyme activities and bacterial communities. Our findings provide insights into how soil responds to the concurrent impacts of snail invasion and soil salinization, establishing some references for future research.

Presently, the essential oils are obtained by hydro-distillation, which demand long extracting time and great energy. Consequently, efficiently obtaining essential oils needs to be considered. In this work, microwave-assisted ionic liquids treatment followed by hydro-distillation (MILT-HD) is used to extract essential oils. The purpose is to use the multivariate analysis model to investigate the effects of process parameters on extraction efficiency and explore the mechanism for enhancing extraction yields. Through multi-objective optimization, optimum parameters are ionic liquid ratio of 70.00%, irradiation time of 6.00 min and irradiation power of 30.00%. Under these conditions, MILT-HD can significantly increase the extraction efficiency. And it can reduce energy demands. Furthermore, the mechanism for efficient extraction is innovatively explored by electrostatic potential analysis and temperature profile. The ionic liquid has a strong interaction with cellulose, and can better absorb microwave energy and quickly convert it into heat. Under the synergistic interactions of ionic liquids-cell wall and ionic liquids-microwave, the MILT-HD can strongly destroy the cell wall structure. It makes the essential oil efficiently diffuse. Based on this work, it provided a way to obtain Forsythiae fructus essential oils efficiently. And It is helpful to improve the comprehensive understanding of the extraction process of MITL-HD.

Green navigation presents a challenge to sustainable mobility. Carbon emissions are a key indicator for evaluating the sustainability of a route. Some methods of green navigation consider the fastest and shortest route to be the least carbon-emitting option, solely from the driver’s perspective. To address this issue, various studies have incorporated road factors into the sustainability evaluation model and designed static route planning algorithms to minimize carbon emissions. However, there has been no comprehensive analysis of carbon emissions from both the road and the driver perspectives, and the influence of a sustainability evaluation using dynamic traffic states has not been considered. In this paper, we propose a carbon emission evaluation model based on the life cycle assessment (LCA) and a dynamic route planning algorithm that focuses on near-real-time traffic states. First, we develop an evaluation model for carbon emissions from both the road and the driver perspectives using a carbon footprint measurement method. Next, we propose a route planning method with both a static calculation and near-real-time adjustment to minimize carbon emissions. Finally, we select three cases from South China with different characteristics to verify the effectiveness of our model and algorithm. This evaluation model calculates the carbon emissions caused by all parties involved, providing a comprehensive assessment of the total carbon emissions generated by traffic. This approach addresses the problem of traditional route planning, which often fails to account for the influences of variable traffic conditions on the greenest route. We verify the effectiveness of the greenest navigation algorithm and near-real-time green navigation and apply these two aspects to cases where the greenest route is compared with other common navigation results from different dimensions. We compare carbon emissions from vehicles and roads from electric vehicles and gasoline-powered vehicles. If an electric vehicle is equipped with a wind power generator, the proportion of the vehicle’s carbon emissions will be very small. For other vehicle types, the carbon emissions will be more than 1000 times the road emissions.

Abstract Background As an immune enhancer, Nocardia rubra cell‐wall skeleton (Nr‐CWS) has been used to treat persistent human papillomavirus infection and cervical precancerous lesions. However, it is still unclear whether it can be used to treat cervical carcinoma. Methods In our study, the aim was to determine whether Nr‐CWS affects the apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages in vivo and in vitro. Results The experimental results showed that Nr‐CWS can promote the activity of dendritic cells and macrophages and reduce their apoptosis. It also increased the cytokines IL‐6, IL‐12, TNF‐ɑ, and IL‐1β secreted by dendritic cells and macrophages and reduced their PD‐L1 expression. In vitro, Nr‐CWS inhibited the proliferation, colony forming ability of HeLa and SiHa cervical carcinoma cell lines cultured with macrophages, and more cells were blocked in G2/M phase. Nr‐CWS promoted TNF‐ɑ/TNFR1/caspase‐8‐mediated apoptosis by increasing macrophages secretion of TNF‐ɑ and inhibited cell migration and invasion regulated by the WNT/β‐catenin‐EMT pathway. Nr‐CWS also reduced the expression of the cervical carcinoma genes E6 and E7 thereby increasing expression of p53 gene and decreasing expression of PD‐L1 gene. In vivo, Nr‐CWS inhibited tumor growth and decreased the expression of E6, E7, PD‐L1, P16, Ki67, and PCNA in tumors. Conclusions Therefore, our results suggest that Nr‐CWS can promote apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages.

ObjectiveFamilial dysalbuminemic hyperthyroxinemia (FDH) has not been thoroughly studied in the Chinese population to date. The clinical characteristics of FDH in Chinese patients were summarized, and the susceptibility of common free thyroxine (FT4) immunoassay methods was evaluated.MethodsThe study included 16 affected patients from eight families with FDH admitted to the First Affiliated Hospital of Zhengzhou University. The published FDH patients of Chinese ethnicity were summarized. Clinical characteristics, genetic information, and thyroid function tests were analyzed. The ratio of FT4 to the upper limit of normal (FT4/ULN) in three test platforms was also compared in patients with R218H ALB mutation from our center.ResultsThe R218H ALB mutation was identified in seven families and the R218S in one family. The mean age of diagnosis was 38.4 ± 19.5 years. Half of the probands (4/8) were misdiagnosed as hyperthyroidism previously. The ratios of serum iodothyronine concentration to ULN in FDH patients with R218S were 8.05–9.74 for TT4, 0.68–1.28 for TT3, and 1.20–1.39 for rT3, respectively. The ratios in patients with R218H were 1.44 ± 0.15, 0.65 ± 0.14, and 0.77 ± 0.18, respectively. The FT4/ULN ratio detected using the Abbott I4000 SR platform was significantly lower than Roche Cobas e801 and Beckman UniCel Dxl 800 Access platforms (P < 0.05) in patients with R218H. In addition, nine Chinese families with FDH were retrieved from the literature, of which eight carried the R218H ALB mutation and one the R218S. The TT4/ULN of approximately 90% of patients (19/21) with R218H was 1.53 ± 0.31; the TT3/ULN of 52.4% of patients (11/21) was 1.49 ± 0.91. In the family with R218S, 45.5% of patients (5/11) underwent TT4 dilution test and the TT4/ULN was 11.70 ± 1.33 and 90.9% (10/11) received TT3 testing and the TT3/ULN was 0.39 ± 0.11.ConclusionsTwo ALB mutations, R218S and R218H, were found in eight Chinese families with FDH in this study, and the latter may be a high-frequency mutation in this population. The serum iodothyronine concentration varies with different mutation forms. The rank order of deviation in measured versus reference FT4 values by different immunoassays (lowest to highest) was Abbott < Roche < Beckman in the FDH patients with R218H.

Optical techniques offer a wide variety of applications as light-matter interactions provide extremely sensitive mechanisms to probe or treat target media. Most of these implementations rely on the usage of ballistic or quasi-ballistic photons to achieve high spatial resolution. However, the inherent scattering nature of light in biological tissues or tissue-like scattering media constitutes a critical obstacle that has restricted the penetration depth of non-scattered photons and hence limited the implementation of most optical techniques for wider applications. In addition, the components of an optical system are usually designed and manufactured for a fixed function or performance. Recent advances in wavefront shaping have demonstrated that scattering- or component-induced phase distortions can be compensated by optimizing the wavefront of the input light pattern through iteration or by conjugating the transmission matrix of the scattering medium. This offers unprecedented opportunities in many applications to achieve controllable optical delivery or detection at depths or dynamically configurable functionalities by using scattering media to substitute conventional optical components. In this article, the recent progress of wavefront shaping in multidisciplinary fields is reviewed, from optical focusing and imaging with scattering media, functionalized devices, modulation of mode coupling, and nonlinearity in multimode fiber to multimode fiber-based applications. Apart from insights into the underlying principles and recent advances in wavefront shaping implementations, practical limitations and roadmap for future development are discussed in depth. Looking back and looking forward, it is believed that wavefront shaping holds a bright future that will open new avenues for noninvasive or minimally invasive optical interactions and arbitrary control inside deep tissues. The high degree of freedom with multiple scattering will also provide unprecedented opportunities to develop novel optical devices based on a single scattering medium (generic or customized) that can outperform traditional optical components.

Photoacoustic microscopy uses multiple wavelengths to measure concentrations of different absorbers. The speed of sound limits the shortest wavelength switching time to sub-microseconds, which is a bottleneck for high-speed broad-spectrum imaging. Via computational separation of overlapped signals, we can break the sound-speed limit on the wavelength switching time. This paper presents a new signal unmixing algorithm named two-step proximal gradient descent. It is advantageous in separating multiple wavelengths with long overlapping and high noise. In the simulation, we can unmix up to nine overlapped signals and successfully separate three overlapped signals with 12-ns delay and 15.9-dB signal-to-noise ratio. We apply this technique to separate three-wavelength photoacoustic images in microvessels. In vivo results show that the algorithm can successfully unmix overlapped multi-wavelength photoacoustic signals, and the unmixed data can improve accuracy in oxygen saturation imaging.

Human pluripotent stem cell–based (hPSC-based) replacement therapy holds great promise for the treatment of Parkinson’s disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we have characterized the single-cell molecular landscape during mDA neuron differentiation. We found that this process recapitulated the development of multiple but adjacent fetal brain regions including the ventral midbrain, the isthmus, and the ventral hindbrain, resulting in a heterogenous donor cell population. We reconstructed the differentiation trajectory of the mDA lineage and identified calsyntenin 2 (CLSTN2) and protein tyrosine phosphatase receptor type O (PTPRO) as specific surface markers of mDA progenitors, which were predictive of mDA neuron differentiation and could facilitate high enrichment of mDA neurons (up to 80%) following progenitor cell sorting and transplantation. Marker-sorted progenitors exhibited higher therapeutic potency in correcting motor deficits of PD mice. Different marker-sorted grafts had a strikingly consistent cellular composition, in which mDA neurons were enriched, while off-target neuron types were mostly depleted, suggesting stable graft outcomes. Our study provides a better understanding of cellular heterogeneity during mDA neuron differentiation and establishes a strategy to generate highly purified donor cells to achieve stable and predictable therapeutic outcomes, raising the prospect of hPSC-based PD cell replacement therapies.

Purple-stem Brassica napus (B. napus) is a phenotype with unique color because of its high anthocyanins content. Anthocyanins are naturally occurring plant pigments that have antioxidants activity and play important role in plant defense against abiotic and biotic stresses. In the present study, drought induced effects on plants were investigated in hydroponically grown seedlings of green stem (GS) and purple stem (PS) genotypes of B. napus. The results of this study showed that the major function of anthocyanins accumulation during drought was to enhance the antioxidant capability and stress tolerance in B. napus plants. Our results showed that drought significantly inhibited the plant growth in terms of decreased biomass accumulation in both genotypes, although marked decline was observed in GS genotype. The reduction in photosynthetic attributes was more noticeable in the GS genotype, whereas the PS genotype showed better performance under drought stress. Under stressful conditions, both the genotype showed excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher levels of antioxidant enzymes activities. Under drought conditions, the GS genotype showed apparent damages on chloroplast deformation like in thylakoid membrane and grana structural distortion and fewer starch grains and bigger plastoglobuli. Moreover, during drought stress, the PS genotype exhibited maximum expression levels of anthocyanins biosynthesis genes and antioxidant enzymes accompanied by higher stress tolerance relative to GS genotype. Based on these findings, it can be concluded that GS genotype found more sensitive to drought stress than the PS genotype. Furthermore this research paper also provides practical guidance for plant biologists who are developing stress-tolerant crops by using anthocyanin biosynthesis or regulatory genes.

BackgroundIn patients with autoimmune encephalitis (AE), the prediction of progression to a critically ill status is challenging but essential. However, there is currently no standard prediction model that comprehensively integrates the disease severity and other clinical features. The clinical assessment scale in autoimmune encephalitis (CASE) and the modified Rankin Scale (mRS) have both been applied for evaluating the severity of AE. Here, by combining the two scales and other clinical characteristics, we aimed to investigate risk factors and construct prediction models for early critical care needs of AE patients.MethodsDefinite and probable AE patients who were admitted to the neurology department of Tongji Hospital between 2013 and 2021 were consecutively enrolled. The CASE and mRS scores were used to evaluate the overall symptom severity at the time of hospital admission. Using logistic regression analysis, we analyzed the association between the total scores of the two scales and critical illness individually and then we evaluated this association in combination with other clinical features to predict early intensive care unit (ICU) admission. Finally, we constructed four prediction models and compared their performances.ResultsOf 234 patients enrolled, forty developed critical illness and were early admitted to the ICU (within 14 days of hospitalization). Four prediction models were generated; the models were named CASE, CASE-plus (CASE + prodromal symptoms + elevated fasting blood glucose + elevated cerebrospinal fluid (CSF) white blood cell (WBC) count), mRS and mRS-plus (mRS + prodromal symptoms + abnormal EEG results + elevated fasting blood glucose + elevated CSF WBC count) and had areas under the ROC curve of 0.850, 0.897, 0.695 and 0.833, respectively. All four models had good calibrations. In general, the models containing “CASE” performed better than those including “mRS”, and the CASE-plus model demonstrated the best performance.ConclusionOverall, the symptom severity at hospital admission, as defined by CASE or mRS, could predict early ICU admission, especially when assessed by CASE. Adding other clinical findings, such as prodromal symptoms, an increased fasting blood glucose level and an increased CSF WBC count, could improve the predictive efficacy.

The COVID-19 pandemic has made the advantages of online knowledge communities with cross-space, time, interpersonal, and other characteristics fully demonstrated. Exploring the configurations of platform incentives to improve knowledge collaboration performance can provide a reference for the efficient and sustainable development of the platforms under the normalization of the COVID-19 pandemic. With the help of the fuzzy set qualitative comparative analysis method, taking the social Q&A platform enterprises as an example, this study analyzed the configurations of platform incentives for the high knowledge collaborative performance from the dimensions of market incentives and social incentives, and the heterogeneity of knowledge capital appreciation and social capital appreciation is also discussed. The results show that each of the platform incentives (virtual currency, cash benefit, community reputation, social identity, skill training, and communication) does not constitute a necessary condition for high performance. There are four and three types of configurations for intellectual capital appreciation and social capital appreciation, respectively. The important findings are that nearly 30% of users may participate in knowledge production based on pure economic benefits, and there may be so-called “get the best deal” behavior. Social identity, community reputation, and skill training have an important incentive effect on knowledge collaboration. Communication supplemented by a little economic incentives can significantly promote the appreciation of social capital.

Optical-resolution photoacoustic microscopy (OR-PAM) enjoys superior spatial resolution and has received intense attention in recent years. The application, however, has been limited to shallow depths because of strong scattering of light in biological tissues. In this work, we propose to achieve deep-penetrating OR-PAM performance by using deep learning enabled image transformation on blurry living mouse vascular images that were acquired with an acoustic-resolution photoacoustic microscopy (AR-PAM) setup. A generative adversarial network (GAN) was trained in this study and improved the imaging lateral resolution of AR-PAM from 54.0 µm to 5.1 µm, comparable to that of a typical OR-PAM (4.7 µm). The feasibility of the network was evaluated with living mouse ear data, producing superior microvasculature images that outperforms blind deconvolution. The generalization of the network was validated with in vivo mouse brain data. Moreover, it was shown experimentally that the deep-learning method can retain high resolution at tissue depths beyond one optical transport mean free path. Whilst it can be further improved, the proposed method provides new horizons to expand the scope of OR-PAM towards deep-tissue imaging and wide applications in biomedicine.

Optogenetics is proved to be a powerful tool for exploring the connection between behavior and neural circuits. The progress greatly benefits from the advances of optical techniques that enable high spatiotemporal resolution for selective single‐neuron stimulation through modulating light. Efficient propagation of modulated light, however, is handicapped by strong optical scattering in biological tissues, which results in inherent tradeoff between penetration depth and resolution. Schemes like graded index (GRIN) lens‐based microendoscopes are developed to yield more confined delivery of light, but tissue damage caused by the insertion of the bulky components cannot be ignored. Herein, an optically selective precise neuron stimulation using an ultrathin multimode fiber (MMF) is demonstrated, which is empowered by optical wavefront shaping to achieve light focusing and rapid raster scanning without mechanical movement at the distal end of the MMF and even through a mouse skull. With this method, primary neurons expressing Chr2 can be regulated spatiotemporally in experiment. Although a lot shall be further improved, the work may open up new venues for noninvasive or minimally invasive all‐optical investigation of neural circuits in used‐to‐be optically inaccessible brain regions.

Inflammation is a double-edged sword that can be induced by various PAMPs, resulting in the control of infection by invading pathogens or injuries. The inflammatory response requires strict and precise control and regulation. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression via translational inhibition or mRNA degradation. However, the role of miRNAs in inflammation induced by flagellin (ligand of TLR5) has yet to be fully determined. In this study, we identified differentially expressed miRNAs in murine bone marrow-derived dendritic cells (BMDCs) between flagellin treatment and medium alone using miRNA microarray. We found that flagellin stimulation downregulated miR-5112 expression in BMDCs and spleen DCs in vitro and in vivo. The overexpression of miR-5112 decreased inflammatory cytokine production, accompanied by a reduction of IKKγ in flagellin-stimulated BMDCs. We demonstrated that miR-5112 could directly target IKKγ to inhibit inflammatory cytokine production. Furthermore, miR-5112 inhibited the inflammatory response induced by flagellin or Salmonella infection in vivo. Interestingly, miR-5112 could also dampen the inflammatory response and alleviate dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. These results suggest that miR-5112 could be a novel therapeutic target for both bacterial infection and DSS-induced colitis model.

ABSTRACT The effect of antiretroviral therapy (ART) on CD4+/CD25hi/CD127low T lymphocyte changes in people living with HIV/AIDS (PLWHA) is still a matter of debate. From October 2015 to December 2019, peripheral blood from 70 cases of PLWHA were collected for the detection of CD4+/CD25hi/CD127low T lymphocytes by flow cytometry. Statistical analysis was performed to detect changes of CD4+/CD25hi/CD127low T lymphocytes in patients with different duration of ART and different treatment effects. We found that the number of CD4+/CD25hi/CD127low T lymphocytes in ART-naive PLWHA were lower than those in healthy volunteers (10.3±٦.٠ cells/uL vs 31.7±8.0 cells/uL, P < 0.05). CD4+/CD25hi/CD127low T lymphocyte counts increased to 17.8±٤.٠ cells/uL 6 months post-ART and 25.0±١١.٩ cells/uL 9 months post-ART, respectively (P < 0.05). There was no significant difference in CD4+/CD25hi/CD127low T lymphocyte counts between PLWHA who reached a complete immune reconstruction after ART and healthy volunteers. The growth of CD4+/CD25hi/CD127low T lymphocyte counts in patients who had baseline CD4 > 200 cells/uL was greater than those who had baseline CD4 ≤ 200 cells/uL (12.6±٤.٦ cells/uL vs 5.6±٥.٠ cells/uL, P = 0.027). CD4+/CD25hi/CD127low T lymphocyte counts were positively correlated with CD4+ T lymphocyte counts (r = 0.923, P < 0.001) and CD4+/CD8+ ratio (r = 0.741, P < 0.001), but were negatively correlated with HIV-VL (r = −0.648, P = 0.000). In conclusion, the results of the present study showed that changes in CD4+/CD25hi/CD127low T lymphocyte counts can be used to assess the effect of ART in PLWHA.