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Multiple sclerosis (MS) is a chronic autoimmune disease in the central nervous system. Forskolin (FSK) is a plant-derived diterpene with excellent immunomodulatory properties and has not been systematically reported for treating MS. This study investigated the therapeutic effects of FSK on cellular and animal MS models and preliminarily explored related mechanisms. The results showed that FSK suppressed the inflammatory response, reduced the expression of STEAP4, and relieved iron deposition in BV-2 cells pretreated by LPS at the cellular level. Meanwhile, at the animal level, FSK treatment halted the progression of experimental autoimmune encephalomyelitis (EAE), alleviated the damage at the lesion sites, reduced the concentration of proinflammatory factors in peripheral blood, and inhibited the immune response of peripheral immune organs in EAE mice. Besides, FSK treatment decreased the expression of STEAP4 in the spinal cord and effectively restored the iron balance in the brain, spinal cord, and serum of EAE mice. Further investigation showed that FSK can reduce IL-17 expression, prevent the differentiation of TH17 cells, and inhibit the calcium signaling pathway. Thus, these results demonstrate that FSK may have the potential to treat MS clinically.

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Despite advances in deep learning for plant leaf disease recognition, accurately distinguishing morphological features under varying environmental conditions continues to pose significant challenges. Traditional deep learning models often fail to effectively merge local and global information, especially in small-scale datasets, impairing performance and elevating training costs. Focusing on citrus diseases, we propose an improved FasterViT Model, an advanced hybrid CNN-ViT framework that builds upon the FasterViT model. The proposed model seamlessly integrates CNN's rapid local learning capabilities with ViT's global information processing strength, thereby effectively extracting complex textures and morphological features from images. Cross-stage alternating Mixup and Cutout methods are strategically employed to enhance model robustness and generalization capabilities, particularly valuable for fast learning on small-scale datasets by simulating a more diverse training environment. Triplet Attention and AdaptiveAvgPool mechanisms are utilized to reduce training costs and optimize training performance. The proposed model is tested on both our specially constructed small-scale citrus disease dataset called in-field small dataset and the comprehensive PlantVillage dataset. The experimental results demonstrated that the model exhibits the capability of fast learning and adaptation to small sample training in plant disease detection tasks, and demonstrates the effectiveness of our improvement approach in improving model accuracy and reducing training costs. Additionally, its exemplary performance in transfer learning scenarios underscores its adaptability and broad applicability. This study not only highlights the efficacy of the improved FasterViT model in addressing the complexities of plant disease image recognition but also pioneers a new paradigm for developing efficient, scalable, and robust classification systems.

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Increasing planting density is a key strategy for enhancing maize yields1-3. An ideotype for dense planting requires a 'smart canopy' with leaf angles at different canopy layers differentially optimized to maximize light interception and photosynthesis4-6, among other features. Here we identified leaf angle architecture of smart canopy 1 (lac1), a natural mutant with upright upper leaves, less erect middle leaves and relatively flat lower leaves. lac1 has improved photosynthetic capacity and attenuated responses to shade under dense planting. lac1 encodes a brassinosteroid C-22 hydroxylase that predominantly regulates upper leaf angle. Phytochrome A photoreceptors accumulate in shade and interact with the transcription factor RAVL1 to promote its degradation via the 26S proteasome, thereby inhibiting activation of lac1 by RAVL1 and decreasing brassinosteroid levels. This ultimately decreases upper leaf angle in dense fields. Large-scale field trials demonstrate that lac1 boosts maize yields under high planting densities. To quickly introduce lac1 into breeding germplasm, we transformed a haploid inducer and recovered homozygous lac1 edits from 20 diverse inbred lines. The tested doubled haploids uniformly acquired smart-canopy-like plant architecture. We provide an important target and an accelerated strategy for developing high-density-tolerant cultivars, with lac1 serving as a genetic chassis for further engineering of a smart canopy in maize.

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The reciprocal coordination between cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver is essential for maintaining cholesterol homeostasis, yet the mechanisms governing the opposing regulation of these processes remain poorly understood. Here, we identify a hormone, Cholesin, which is capable of inhibiting cholesterol synthesis in the liver, leading to a reduction in circulating cholesterol levels. Cholesin is encoded by a gene with a previously unknown function (C7orf50 in humans; 3110082I17Rik in mice). It is secreted from the intestine in response to cholesterol absorption and binds to GPR146, an orphan G-protein-coupled receptor, exerting antagonistic downstream effects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterol synthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effective agent in combating hypercholesterolemia and atherosclerosis.

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CONTEXT: Family caregivers face significant challenges when providing care to individuals with advanced cancer. Spiritual coping strategies may support caregivers in addressing these challenges. OBJECTIVES: We evaluated spiritual coping levels among Chinese family caregivers of patients with advanced cancer and explored associated factors. METHODS: This cross-sectional study recruited 358 family caregivers of patients with advanced cancer. The Spiritual Coping Scale was used to evaluate spiritual coping levels, while various scales, including the Caregiver Reaction Assessment Scale, General Self-Efficacy Scale-Schwarzer, and Perceived Social Support Scale, were used to identify influencing factors. T-tests and analysis of variance were used for group comparisons. Pearson's correlation and multivariate linear regression were used to analyze the associated factors. RESULTS: Chinese family caregivers of patients with advanced cancer had moderate spiritual coping levels. Differences in spiritual coping levels were observed in sex, religion, and the presence or absence of anxiety and depression (p < 0.05). Women and caregivers who identified as religious had higher levels, while those with anxiety or depression had lower levels. Spiritual coping was positively correlated with self-efficacy and spiritual health (p < 0.01). Multiple linear regression analysis revealed that religion, anxiety, depression, self-efficacy, and spiritual health were statistically significant associated factors for spiritual coping scores, explaining 43.3% of the variance in scores (F = 53.769, p < 0.001). CONCLUSION: The spiritual coping of Chinese family caregivers should be considered by health care providers, who should focus on alleviating their anxiety and depression while improving self-efficacy and spiritual health, especially among nonreligious caregivers.

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Problems: Plant Disease diagnosis based on deep learning mechanisms has been extensively studied and applied. However, the complex and dynamic agricultural growth environment results in significant variations in the distribution of state samples, and the lack of sufficient real disease databases weakens the information carried by the samples, posing challenges for accurately training models. Aim: This paper aims to test the feasibility and effectiveness of Denoising Diffusion Probabilistic Models (DDPM), Swin Transformer model, and Transfer Learning in diagnosing citrus diseases with a small sample. Methods: Two training methods are proposed: The Method 1 employs the DDPM to generate synthetic images for data augmentation. The Swin Transformer model is then used for pre-training on the synthetic dataset produced by DDPM, followed by fine-tuning on the original citrus leaf images for disease classification through transfer learning. The Method 2 utilizes the pre-trained Swin Transformer model on the ImageNet dataset and fine-tunes it on the augmented dataset composed of the original and DDPM synthetic images. Results and conclusion: The test results indicate that Method 1 achieved a validation accuracy of 96.3%, while Method 2 achieved a validation accuracy of 99.8%. Both methods effectively addressed the issue of model overfitting when dealing with a small dataset. Additionally, when compared with VGG16, EfficientNet, ShuffleNet, MobileNetV2, and DenseNet121 in citrus disease classification, the experimental results demonstrate the superiority of the proposed methods over existing approaches to a certain extent.

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Reticulocalbin-1 (RCN1) is expressed aberrantly and at a high level in various tumors, including acute myeloid leukemia (AML), yet its impact on AML remains unclear. In this study, we demonstrate that RCN1 knockdown significantly suppresses the viability of bone marrow mononuclear cells (BMMNCs) from AML patients but does not affect the viability of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs) from healthy donors in vitro. Downregulation of RCN1 also reduces the viability of AML cell lines. Further studies showed that the RCN1 knockdown upregulates type I interferon (IFN-1) expression and promotes AML cell pyroptosis through caspase-1 and gasdermin D (GSDMD) signaling. Deletion of the mouse Rcn1 gene inhibits the viability of mouse AML cell lines but not the hematopoiesis of mouse bone marrow. In addition, RCN1 downregulation in human AML cells significantly inhibited tumor growth in the NSG mouse xenograft model. Taken together, our results suggest that RCN1 may be a potential target for AML therapy.

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Ankylosing spondylitis (AS) is clinically characterized by bone fusion that is induced by the pathological formation of extra bone. Unfortunately, the fundamental mechanism and related therapies remain unclear. The loss of SHP-2 (encoded by Ptpn11) in CD4-Cre;Ptpn11f/f mice resulted in the induction of AS-like pathological characteristics, including spontaneous cartilage and bone lesions, kyphosis, and arthritis. Hence, this mouse was utilized as an AS model in this study. As one of the basic physical fields, the magnetic field (MF) has been proven to be an effective treatment method for articular cartilage degeneration. In this study, the effects of a rotating magnetic field (RMF; 0.2 T, 4 Hz) on an AS-like mouse model were investigated. The RMF treatment (2 h/d, 0.2 T, 4 Hz) was performed on AS mice from two months after birth until the day before sampling. The murine specimens were subjected to transcriptomics, immunomics, and metabolomics analyses, combined with molecular and pathological experiments. The results demonstrated that the mitigation of inflammatory deterioration resulted in an increase in functional osteogenesis and a decrease in dysfunctional osteolysis due to the maintenance of bone homeostasis via the RANKL/RANK/OPG signaling pathway. Additionally, by regulating the ratio of CD4+ and CD8+ T-cells, RMF treatment rebalanced the immune microenvironment in skeletal tissue. It has been observed that RMF interventions have the potential to alleviate AS, including by decreasing pathogenicity and preventing disease initiation. Consequently, RMF, as a moderately physical therapeutic strategy, could be considered to alleviate the degradation of cartilage and bone tissue in AS and as a potential option to halt the progression of AS.

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We demonstrated a two-dimensional vector displacement (bending) sensor with high angular resolution based on Vernier effect generated by two cascaded Fabry-Perot interferometers (FPI) in a seven-core fiber (SCF). To form the FPI, plane-shaped refractive index modulations are fabricated as the reflection mirrors in the SCF using slit-beam shaping and femtosecond laser direct writing. Three pairs of cascaded FPIs are fabricated in the center core and the two non-diagonal edge cores of the SCF and applied to the vector displacement measurement. The proposed sensor exhibits high displacement sensitivity with significant direction dependence. The magnitude and direction of the fiber displacement can be obtained via monitoring the wavelength shifts. Moreover, the source fluctuations and the temperature cross-sensitivity can be referenced out by monitoring the bending-insensitive FPI of the center core.

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We propose and fabricate a high-sensitivity vector vibration accelerometer with a multicore fiber Bragg grating Fabry-Perot (FBG-FP) structure. The acceleration sensitivities of the FBG and FBG-FP are 0.15 and 1.26 V/g, respectively. After packaging, the acceleration sensitivity of the FBG-FP is further improved to 6.89 V/g, which is 45.9 times higher than that of the FBG. The resonant frequency of the accelerometer increases from 30 to 86 Hz. Both the sensitivity and resonant frequency of the accelerometer are improved. Owing to the asymmetry of the outer core of the multicore fiber, high-sensitivity two-dimensional vector acceleration sensing can be realized.

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Various products made from biodegradable polymers have been increasing rapidly in the market since the use of non-biodegradable materials has been banned, particularly for the disabled packaging materials. Burning remains the most popular method that is increasingly used in treating city wastes. The impact of these polymers on environmental during thermal degradation and combustion is an important issue for city waste management. In this work, the thermal degradation and combustion behaviours of the most popular synthetic biodegradable polymers in the market, poly(lactide acid) (PLA), poly(e-caprolactone) (PCL), poly(butylene succinate) (PBS), poly(butylene adipate-co-terephthalate) (PBAT) and polyhydroxyalkenoates (PHA), are investigated. Both isothermal and non-isothermal thermal decomposition in oxygen and nitrogen environment were studied using thermogravimetric analysis combining with differential scanning calorimeter and coupled with Fourier transform infrared spectroscopy and gas chromatograph/mass spectroscopy. The combustion behaviour was investigated by a combustion colorimeter. The study results show that thermal degradation temperatures are PCL > PBS > PLA > PBAT > PHA. The thermal decomposition of all the polyesters started from scission reaction (cis-elimination), and then a stereoselective cis-elimination, which resulted in the formation of trans-crotonic acid and its oligomers. They all decomposed into CO2 and water in excess oxygen environment above 800°C. Various chemical products with smaller molecules were detected under oxygen-free conditions, including oligomers and unsaturated carboxylic acid. The order of the total heat release of the materials from high to low is as follows: PHA > PCL > PBAT > PBS > PLA. The combustion values of these polyesters are lower than those of polyolefins; thus, they will not damage furnace used currently. The results provide some important and useful data for managing these new city waste.

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Objective: Pre-eclampsia (PE) complicated by fetal growth restriction (FGR) increases both perinatal mortality and the incidence of preterm birth and neonatal asphyxia. Because ultrasound measurements are bone markers, soft tissues, such as fetal fat and muscle, are ignored, and the selection of section surface and the influence of fetal position can lead to estimation errors. The early detection of FGR is not easy, resulting in a relative delay in intervention. It is assumed that FGR complicated with PE can be predicted by laboratory and clinical indicators. The present study adopts an artificial neural network (ANN) to assess the effect and predictive value of changes in maternal peripheral blood parameters and clinical indicators on the perinatal outcomes in patients with PE complicated by FGR. Methods: This study used a retrospective case-control approach. The correlation between maternal peripheral blood parameters and perinatal outcomes in pregnant patients with PE complicated by FGR was retrospectively analyzed, and an ANN was constructed to assess the value of the changes in maternal blood parameters in predicting the occurrence of PE complicated by FGR and adverse perinatal outcomes. Results: A total of 15 factors-maternal age, pre-pregnancy body mass index, inflammatory markers (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio), coagulation parameters (prothrombin time and thrombin time), lipid parameters (high-density lipoprotein, low-density lipoprotein, and triglyceride counts), platelet parameters (mean platelet volume and plateletcrit), uric acid, lactate dehydrogenase, and total bile acids-were correlated with PE complicated by FGR. A total of six ANNs were constructed with the adoption of these parameters. The accuracy, sensitivity, and specificity of predicting the occurrence of the following diseases and adverse outcomes were respectively as follows: 84.3%, 97.7%, and 78% for PE complicated by FGR; 76.3%, 97.3%, and 68% for provider-initiated preterm births,; 81.9%, 97.2%, and 51% for predicting the severity of FGR; 80.3%, 92.9%, and 79% for premature rupture of membranes; 80.1%, 92.3%, and 79% for postpartum hemorrhage; and 77.6%, 92.3%, and 76% for fetal distress. Conclusion: An ANN model based on maternal peripheral blood parameters has a good predictive value for the occurrence of PE complicated by FGR and its adverse perinatal outcomes, such as the severity of FGR and preterm births in these patients.

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The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). In vivo and vitro tests were used to assess tumor cell inhibition. In vitro, the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response in vivo and in vitro, and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC.

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In this Letter, we propose and experimentally demonstrate fiber Bragg grating (FBG) fabrication in a flexible and stretchable coreless polymer optical fiber. The flexible polymer optical fiber is prepared with polydimethylsiloxane (PDMS). Femtosecond laser direct writing and slit beam shaping are used to form periodic grating structures in the fiber. The fabricated FBG exhibits a large strain measurement range and a blueshift response to temperature. Moreover, it offers low humidity sensitivity due to its low permeability toward water vapor. Taking advantage of the unique sensing performances of the PDMS fiber, the proposed FBG has considerable advantages over the traditional silica FBG devices for strain and temperature sensing.

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We propose an ultrahigh-order fiber Bragg grating (UHO-FBG) containing dense resonants and its application as a novel filtering device in multi-wavelength lasers. The UHO-FBG is fabricated by femtosecond laser plane-by-plane direct inscription. Thanks to the plane-by-plane inscription, high-order Bragg resonances can be formed with multiple reflectance peaks of comparable reflectance in the range of the fiber operating bandwidth and without the transmission depression of long-period gratings in the transmission spectrum. We also experimentally demonstrate the use of UHO-FBG pairs in a distributed Bragg reflector laser, enabling the excitation of multi-wavelength lasers.

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This study aimed to translate the Spiritual Perspectives Scale (SPS) into a Mandarin Chinese version (C-SPS) and evaluate its psychometric properties among 154 palliative care nurses from twelve community healthcare centres in Shanghai, China. Exploratory factor analysis suggested two factors (spiritually related activities and spiritual beliefs), accounting for 67.49% of the total variance. The Cronbach's α of the total C-SPS score was 0.89, and its split-half coefficient (Spearman-Brown reliability coefficient) was 0.72. The C-SPS showed consistently acceptable psychometric properties of reliability and validity. It can be used to evaluate the level of spiritual perspectives of nurses in China.

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BACKGROUND: The morbidity and mortality of community-acquired pneumonia are relatively high, but many pneumonia pathogens cannot be identified accurately. As a new pathogen detection technology, metagenomic next-generation sequencing (mNGS) has been applied more and more clinically. We aimed to evaluate the diagnostic significance of mNGS for community-acquired pneumonia (CAP) in the south of China. METHODS: Our study selected CAP patients who visited the 3rd Xiangya Hospital from May 2019 to April 2021. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected using mNGS and traditional microbiological culture. mNGS group: detected by both mNGS and BALF culture; control group: detected only by BALF or sputum culture. The diagnostic performance of pathogens and the antibiotic adjustments were compared within mNGS group. RESULTS: The incidence of acute respiratory distress syndrome (ARDS) was 28.3% in the mNGS group and 17.3% in the control group. Within the mNGS group, the positive rate of pathogens detected by mNGS was 64%, thus by BALF culture was only 28%. Pathogens detected by mNGS were consisted of bacteria (55%), fungi (18%), special pathogens (18%), and viruses (9%). The most detected pathogen by mNGS was Chlamydia psittaci. Among the pathogen-positive cases, 26% was not pathogen-covered by empirical antibiotics, so most of which were made an antibiotic adjustment. CONCLUSIONS: mNGS can detect pathogens in a more timely and accurate manner and assist clinicians to adjust antibiotics in time. Therefore, we recommend mNGS as the complementary diagnosis of severe pneumonia or complicated infections.

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In this Letter, a helical-sampled fiber Bragg gratings (HSFBGs) fabrication using a femtosecond laser point-by-point (PBP) technique is proposed. The unique helical structure generates sampled gratings owing to its periodicity. A simple, single-step method for inscription of the sampled gratings is described. The effects of geometrical parameters, including length of grating, helical diameter, helical pitch, and off-axis distance on the resonances are studied, and a series of comb-like spectra are obtained.

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BACKGROUND: Rapid and reliable diagnostic methods for Aspergillus fumigatus infection are urgently needed. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 13a (Cas13a) has high sensitivity and specificity in the diagnosis of viral infection. However, its potential use in detecting A. fumigatus remains unexplored. A highly sensitive and specific method using the CRISPR/Cas13a system was developed for the reliable and rapid detection of A. fumigatus. METHODS: The conserved internal transcribed spacer (ITS) region of A. fumigatus was used to design CRISPR-derived RNA (crRNA) and the corresponding recombinase polymerase amplification (RPA) primer sequence with the T7 promoter for the CRISPR assay. Twenty-five clinical isolates and 43 bronchoalveolar lavage fluid (BALF) remaining from routine examinations of patients with confirmed pulmonary aspergillosis were collected to further validate the CRISPR assay. RESULTS: No amplification signal was observed when genomic DNA from closely clinically related Aspergillus species, such as Aspergillus flavus, Aspergillus niger, and Aspergillus terreus, as well as Monascus purpureus Went and Escherichia coli, was tested by this assay, and the detection limit for A. fumigatus was 3 copies in a single reaction system. Validation experiments using the 25 clinical isolates demonstrated 91.7% specificity for the A. fumigatus section, and the sensitivity was 100% when first-generation sequencing was used as the standard. There was no significant difference between the PCR and CRISPR methods (P = 1.0), and the diagnosis results of the two methods were consistent (Kappa = 0.459, P = 0.003). CONCLUSION: The study offers a new validated CRISPR/Cas13a technique for A. fumigatus detection, providing a simple, rapid and affordable test that is ready for application in the diagnosis of A. fumigatus infection.

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A two-dimensional vector bending sensor that is both compact and simple is proposed and demonstrated, based on an edge-core cladding-type fiber Bragg grating (ECLFBG) inscribed in an edge-core. The ECLFBG is written parallel to the edge-core using a femtosecond laser point-by-point technique. The reflection spectrum of this ECLFBG varies significantly depending on the magnitude and direction of the fiber's bend. Combining the trend and sensitivity of the wavelength shift and reflection intensity variations of the ECLFBG, the bending magnitude and direction can be measured simultaneously.