Single-shot inline holography using a physics-aware diffusion model: errata.

We present an erratum to our paper [Opt. Express32, 10444 (2024)10.1364/OE.517233]. This erratum aims to address an unintentional error in the methodology presented in Part 3.1. The error may lead to confusion among readers, and we provide additional clarification to ensure a comprehensive understanding of the technique. It is important to note that these corrections do not affect the results or conclusions of the original work.

Intermittent blood flow restriction with low-load resistance training for older adults with knee osteoarthritis: a randomized, controlled, non-inferiority trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disorder characterized by pain and functional impairment. Blood flow restriction (BFR) with low-load resistance training (LLRT) demonstrates a similar improvement in clinical outcomes to high-load resistance training (HLRT) in treating KOA. It has not been established whether intermittent blood flow restriction (iBFR) with LLRT can lead to clinical outcomes that are comparable to those produced by continuous blood flow restriction (cBFR) with LLRT and HLRT. The aim of the proposed study is to evaluate the efficacy of iBFR with LLRT on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence in KOA patients. METHODS: This is a three-arm, non-inferiority, randomized controlled trial utilizing blinded assessors. Two hundred thirteen participants will be randomly allocated to one of the following three groups: iBFR group-receiving 4 months of LLRT with iBFR, twice weekly (n = 71); cBFR group-receiving 4 months of LLRT with cBFR, twice weekly (n = 71); or HLRT group-receiving 4 months of HLRT without BFR, twice weekly (n = 71). The primary outcome is pain. The secondary outcomes include the WOMAC, muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence. Pain and WOMAC will be measured at the baseline and 4 and 12 months after randomizations. Muscle strength, muscle mass, and physical function will be measured at the baseline and 4 months after randomizations. The perceptions of discomfort and effort will be measured during the first and final sessions. DISCUSSION: BFR with LLRT has a similar improvement in clinical outcomes as HLRT. However, cBFR may cause elevated ratings of perceived exertion and local discomfort, compromising patient tolerability and treatment adherence. If iBFR with LLRT could produce improvement in clinical outcomes analogous to those of HLRT and iBFR with LLRT, it could be considered an alternative approach for treating patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072820. Registered on June 26, 2023.

Association between passing return-to-sport testing and re-injury risk in patients after anterior cruciate ligament reconstruction surgery: a systematic review and meta-analysis.

Background: Inconsistent results have been obtained regarding the association between return-to-sport (RTS) testing and the risk of subsequent re-injury following anterior cruciate ligament reconstruction (ACLR). We therefore conducted a systematic review and meta-analysis to assess the potential association between passing of RTS and the risk of re-injury for patients after ACLR. Methods: This meta-analysis was registered in INPLASY with the registration number INPLASY202360027. The electronic databases MedLine, EmBase, and the Cochrane library were systematically searched to identify eligible studies from their inception up to September 2023. The investigated outcomes included knee injury, secondary ACL, contralateral ACL injury, and graft rupture. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Results: A total number of nine studies involving 1410 individuals were selected for the final quantitative analysis. We noted that passing RTS test was not associated with the risk of subsequent knee injury (OR: 0.95; 95% CI: 0.28-3.21; P = 0.929), secondary ACL injury (OR: 0.98; 95% CI: 0.55-1.75; P = 0.945), and contralateral ACL injury (OR: 1.53; 95% CI: 0.63-3.71; P = 0.347). However, the risk of graft rupture was significantly reduced (OR: 0.49; 95% CI: 0.33-0.75; P = 0.001). Conclusions: This study found that passing RTS test was not associated with the risk of subsequent knee injury, secondary ACL injury, and contralateral ACL injury, while it was associated with a lower risk of graft rupture. Thus, it is recommended that patients after ACLR pass an RTS test in clinical settings.

Single-shot inline holography using a physics-aware diffusion model.

Among holographic imaging configurations, inline holography excels in its compact design and portability, making it the preferred choice for on-site or field applications with unique imaging requirements. However, effectively holographic reconstruction from a single-shot measurement remains a challenge. While several approaches have been proposed, our novel unsupervised algorithm, the physics-aware diffusion model for digital holographic reconstruction (PadDH), offers distinct advantages. By seamlessly integrating physical information with a pre-trained diffusion model, PadDH overcomes the need for a holographic training dataset and significantly reduces the number of parameters involved. Through comprehensive experiments using both synthetic and experimental data, we validate the capabilities of PadDH in reducing twin-image contamination and generating high-quality reconstructions. Our work represents significant advancements in unsupervised holographic imaging by harnessing the full potential of the pre-trained diffusion prior.

Deep learning based ultrasound analysis facilitates precise distinction between parotid pleomorphic adenoma and Warthin tumor.

Background: Pleomorphic adenoma (PA), often with the benign-like imaging appearances similar to Warthin tumor (WT), however, is a potentially malignant tumor with a high recurrence rate. It is worse that pathological fine-needle aspiration cytology (FNAC) is difficult to distinguish PA and WT for inexperienced pathologists. This study employed deep learning (DL) technology, which effectively utilized ultrasound images, to provide a reliable approach for discriminating PA from WT. Methods: 488 surgically confirmed patients, including 266 with PA and 222 with WT, were enrolled in this study. Two experienced ultrasound physicians independently evaluated all images to differentiate between PA and WT. The diagnostic performance of preoperative FNAC was also evaluated. During the DL study, all ultrasound images were randomly divided into training (70%), validation (20%), and test (10%) sets. Furthermore, ultrasound images that could not be diagnosed by FNAC were also randomly allocated to training (60%), validation (20%), and test (20%) sets. Five DL models were developed to classify ultrasound images as PA or WT. The robustness of these models was assessed using five-fold cross-validation. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique was employed to visualize the region of interest in the DL models. Results: In Grad-CAM analysis, the DL models accurately identified the mass as the region of interest. The area under the receiver operating characteristic curve (AUROC) of the two ultrasound physicians were 0.351 and 0.598, and FNAC achieved an AUROC of only 0.721. Meanwhile, for DL models, the AUROC value for discriminating between PA and WT in the test set was from 0.828 to 0.908. ResNet50 demonstrated the optimal performance with an AUROC of 0.908, an accuracy of 0.833, a sensitivity of 0.736, and a specificity of 0.904. In the test set of cases that FNAC failed to provide a diagnosis, DenseNet121 demonstrated the optimal performance with an AUROC of 0.897, an accuracy of 0.806, a sensitivity of 0.789, and a specificity of 0.824. Conclusion: For the discrimination of PA and WT, DL models are superior to ultrasound and FNAC, thereby facilitating surgeons in making informed decisions regarding the most appropriate surgical approach.

Novel LIPA-Targeted Therapy for Treating Ovarian Cancer.

Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41. However, the role of LIPA and theutility of ERX-41 to treat OCa remain unknown. Expression analysis using the TNMplot web tool, TCGA data sets, and immunohistochemistry analysis using a tumor tissue array showed that LIPA is highly expressed in OCa tissues, compared to normal tissues. ERX-41 treatment significantly reduced the cell viability and colony formation ability and promoted the apoptosis of OCa cells. Mechanistic studies revealed a robust and consistent induction of ERS markers, including CHOP, elF2α, PERK, and ATF4, upon ERX-41 treatment. In xenograft and PDX studies, ERX-41 treatment resulted in a significant reduction in tumor growth. Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of ERS induction, which could be exploited to treat heterogeneity in OCa.

Harmonizing international quality standards for Andrographis paniculata: A comparative analysis of content determination methods across pharmacopeias.

The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.

Home-based exercise program and Health education in patients with patellofemoral pain: a randomized controlled trial.

BACKGROUND: Patellofemoral pain (PFP) is one of the most common disorders of the knee joint. Home-based exercise is an effective intervention to achieve self-management for chronic diseases. This study evaluated the effects of home-based exercise and health education in patients with PFP. METHODS: Patients who had PFP were randomly allocated to an intervention group (IG) or control group (CG). Patients in the IG received a 6-week tailored home-based exercise program with health education via remote support, while patients in the CG group only received health education. Clinical outcomes were compared using the Anterior Knee Pain Scale (AKPS) to measure function and the Visual Analog Scale (VAS) to measure "worst pain" and "pain with daily activity". Muscle strength was measured according to the peak torque of the knee muscles using an isokinetic system. RESULTS: Among a total of 112 participants screened for eligibility, 38 were randomized and analyzed, including 19 participants in the intervention group and 19 participants in the control group. There were no significant differences in baseline characteristics between the groups. At 6-week follow-up, the intervention group showed a greater worst pain reduction (between-group difference, -19.3 [95%CI, -23.2 to -15.5]; P < 0.01) and pain with daily activity (between-group difference, -22.9 [95%CI, -28.3 to -17.4]; P < 0.01) than the control group. Similarly, the intervention group had better improvements in AKPS (between-group difference, 9.0 [95%CI, 4.1 to 13.9]; P < 0.01) and knee extensor strength (between-group difference, 20.1 [95%CI, 14.5 to 25.8]; P < 0.01), compared to the control group. No adverse events were reported. CONCLUSION: Home-based exercise and health education resulted in less pain, better function, and higher knee muscle strength compared with no exercise in patients with PFP. A large randomized controlled trial with long-term follow-up is required to confirm these findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200056224 ( https://www.chictr.org.cn/showproj.aspx?proj=135506 ). Registered on February 1, 2022.

Coordination of m6A mRNA Methylation and Gene Transcriptome in Sugarcane Response to Drought Stress.

The N6-methyladenosine (m6A) methylation of mRNA is involved in biological processes essential for plant growth. To explore the m6A modification of sugarcane and reveal its regulatory function, methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to construct the m6A map of sugarcane. In this study, m6A sites of sugarcane transcriptome were significantly enriched around the stop codon and within 3'-untranslated regions (3'UTR). Gene ontology (GO) analysis showed that the m6A modification genes are associated with metabolic biosynthesis. In addition, the m6A modification of drought-resistant transcript mRNA increased significantly under drought (DR) treatment, resulting in enhanced mRNA stability, which is involved in regulating sugarcane drought resistance. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that differentially methylated peak (DMP) modification of differentially expressed genes (DEGs) in DR were particularly associated with abscisic acid (ABA) biosynthesis. The upregulated genes were significantly enriched in the ABA metabolism, ethylene response, fatty acid metabolism, and negative regulation of the abscisic acid activation signaling pathway. These findings provide a basis and resource for sugarcane RNA epigenetic studies and further increase our knowledge of the functions of m6A modifications in RNA under abiotic stress.

Comparative transcriptomic analyses of two sugarcane Saccharum L. cultivars differing in drought tolerance.

Sugarcane (Saccharum spp.) is an important cash crop, and drought is an important factors limiting its yield. To study the drought resistance mechanism of sugarcane, the transcriptomes of two sugarcane varieties with different levels of drought resistance were compared under different water shortage levels. The results showed that the transcriptomes of the two varieties were significantly different. The differentially expressed genes were enriched in starch and sucrose metabolism, linoleic acid metabolism, glycolysis/gluconeogenesis, and glyoxylate and dicarboxylate metabolic pathways. Unique trend genes of the variety with strong drought resistance (F172) were significantly enriched in photosynthesis, mitogen-activated protein kinases signaling pathway, biosynthesis of various plant secondary metabolites, and cyanoamino acid metabolism pathways. Weighted correlation network analysis indicated that the blue4 and plum1 modules correlated with drought conditions, whereas the tan and salmon4 modules correlated with variety. The unique trend genes expressed in F172 and mapped to the blue4 module were enriched in photosynthesis, purine metabolism, starch and sucrose metabolism, beta-alanine metabolism, photosynthesis-antenna proteins, and plant hormone signal transduction pathways. The expression of genes involved in the photosynthesis-antenna protein and photosynthesis pathways decreased in response to water deficit, indicating that reducing photosynthesis might be a means for sugarcane to respond to drought stress. The results of this study provide insights into drought resistance mechanisms in plants, and the related genes and metabolic pathways identified may be helpful for sugarcane breeding in the future.

Loss of SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer.

Tumor mutational burden and heterogeneity has been suggested to fuel resistance to many targeted therapies. The cytosine deaminase APOBEC proteins have been implicated in the mutational signatures of more than 70% of human cancers. However, the mechanism underlying how cancer cells hijack the APOBEC mediated mutagenesis machinery to promote tumor heterogeneity, and thereby foster therapy resistance remains unclear. We identify SYNCRIP as an endogenous molecular brake which suppresses APOBEC-driven mutagenesis in prostate cancer (PCa). Overactivated APOBEC3B, in SYNCRIP-deficient PCa cells, is a key mutator, representing the molecular source of driver mutations in some frequently mutated genes in PCa, including FOXA1, EP300. Functional screening identifies eight crucial drivers for androgen receptor (AR)-targeted therapy resistance in PCa that are mutated by APOBEC3B: BRD7, CBX8, EP300, FOXA1, HDAC5, HSF4, STAT3, and AR. These results uncover a cell-intrinsic mechanism that unleashes APOBEC-driven mutagenesis, which plays a significant role in conferring AR-targeted therapy resistance in PCa.

New insights into the distribution, potential source and risk of microplastics in Qinghai-Tibet Plateau.

Microplastics (MPs) as emerging contaminants have become a major global concern, however, the distribution and origin of MPs in Qinghai-Tibet Plateau (QTP) and their impacts on ecosystem are poorly known. Hence, we systematically evaluated the profile of MPs on the representative metropolitan locations of Lhasa and Huangshui Rivers and the scenic sites of Namco and Qinghai Lake. The average abundance of MPs in the water samples was 7020 items/m3, which was 34 and 52 times higher than those for the sediment (206.7 items/m3) and soil samples (134.7 items/m3), respectively. Huangshui River had the highest levels, followed by Qinghai Lake, Lhasa River and Namco. Human activities rather than altitude and salinity impacted the distribution of MPs in those areas. Besides the consumption of plastic products by locals and tourists, laundry wastewater and exogenous tributary inputs, the unique prayer flag culture also contributed to the MPs emission in QTP. Notably, the stability and fragment of MPs were crucial for their fate. Multiple assessment models were employed to evaluate the risk of MPs. PERI model took MP concentration, background value and toxicity into account, comprehensively describing the risk differences of each site. The large PVC proportion in Qinghai Lake posed the highest risk. Furthermore, concerns should be raised about PVC, PE and PET in Lhasa and Huangshui Rivers, and PC in Namco Lake. Risk quotient suggested that aged MPs in sediments slowly released biotoxic DEHP and should be cleaned up promptly. The findings offer baseline data of MPs in QTP and ecological risks, providing important support for the prioritization of future control measures.

Ectopic JAK-STAT activation enables the transition to a stem-like and multilineage state conferring AR-targeted therapy resistance.

Emerging evidence indicates that various cancers can gain resistance to targeted therapies by acquiring lineage plasticity. Although various genomic and transcriptomic aberrations correlate with lineage plasticity, the molecular mechanisms enabling the acquisition of lineage plasticity have not been fully elucidated. We reveal that Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling is a crucial executor in promoting lineage plasticity-driven androgen receptor (AR)-targeted therapy resistance in prostate cancer. Importantly, ectopic JAK-STAT activation is specifically required for the resistance of stem-like subclones expressing multilineage transcriptional programs but not subclones exclusively expressing the neuroendocrine-like lineage program. Both genetic and pharmaceutical inhibition of JAK-STAT signaling resensitizes resistant tumors to AR-targeted therapy. Together, these results suggest that JAK-STAT are compelling therapeutic targets for overcoming lineage plasticity-driven AR-targeted therapy resistance.

Comparative Transcriptome Analysis of Two Sugarcane Cultivars in Response to Paclobutrazol Treatment.

Sugarcane is an important crop across the globe, and the rapid multiplication of excellent cultivars is an important object of the sugarcane industry. As one of the plant growth regulators, paclobutrazol (PBZ) has been frequently used in the tissue culture of sugarcane seedlings. However, little is known about the molecular mechanisms of response to PBZ in this crop. Here, we performed a comparative transcriptome analysis between sensitive (LC05-136) and non-sensitive (GGZ001) sugarcane cultivars treated by PBZ at three time points (0 d, 10 d, and 30 d) using RNA sequencing (RNA-Seq). The results showed that approximately 70.36 Mb of clean data for each sample were generated and assembled into 239,212 unigenes. A total of 6108 and 4404 differentially expressed genes (DEGs) were identified within the sensitive and non-sensitive sugarcane cultivars, respectively. Among them, DEGs in LC05-136 were most significantly enriched in the photosynthesis and valine, leucine and isoleucine degradation pathways, while in GGZ001, DEGs associated with ion channels and plant-pathogen interaction were mainly observed. Notably, many interesting genes, including those encoding putative regulators, key components of photosynthesis, amino acids degradation and glutamatergic synapse, were identified, revealing their importance in the response of sugarcane to PBZ. Furthermore, the expressions of sixteen selected DEGs were tested by quantitative reverse transcription PCR (RT-qPCR), confirming the reliability of the RNA-seq data used in this study. These results provide valuable information regarding the transcriptome changes in sugarcane treated by PBZ and provide an insight into understanding the molecular mechanisms underlying the resistance to PBZ in sugarcane.

Loss of NSE-4 Perturbs Genome Stability and DNA Repair in Caenorhabditis elegans.

The Structural Maintenance of Chromosomes (SMC) complex plays an important role in maintaining chromosome integrity, in which the SMC5/6 complex occupies a central position by facilitating mitotic and meiotic processes as well as DNA repair. NSE-4 Kleisin is critical for both the organization and function of the SMC5/6 complex, bridging NSE1 and NSE3 (MAGE related) with the head domains of the SMC5 and SMC6 proteins. Despite the conservation in protein sequence, no functional relevance of the NSE-4 homologous protein (NSE-4) in Caenorhabditis elegans has been reported. Here, we demonstrated the essential role of C. elegans NSE-4 in genome maintenance and DNA repair. Our results showed that NSE-4 is essential for the maintenance of chromosomal structure and repair of a range of chemically induced DNA damage. Furthermore, NSE-4 is involved in inter-sister repair during meiosis. NSE-4 localizes on the chromosome and is indispensable for the localization of NSE-1. Collectively, our data from this study provide further insight into the evolutionary conservation and diversification of NSE-4 function in the SMC-5/6 complex.

Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress.

Triple-negative breast cancer (TNBC) has a poor clinical outcome, due to a lack of actionable therapeutic targets. Herein we define lysosomal acid lipase A (LIPA) as a viable molecular target in TNBC and identify a stereospecific small molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic reticulum (ER) stress resulting in cell death, and this effect is on target as evidenced by specific LIPA mutations providing resistance. Importantly, we demonstrate that ERX-41 activity is independent of LIPA lipase function but dependent on its ER localization. Mechanistically, ERX-41 binding of LIPA decreases expression of multiple ER-resident proteins involved in protein folding. This targeted vulnerability has a large therapeutic window, with no adverse effects either on normal mammary epithelial cells or in mice. Our study implicates a targeted strategy for solid tumors, including breast, brain, pancreatic and ovarian, whereby small, orally bioavailable molecules targeting LIPA block protein folding, induce ER stress and result in tumor cell death.

Distribution, influence factors, and biotoxicity of environmentally persistent free radical in soil at a typical coking plant.

Environmentally persistent free radicals (EPFRs) are emerging pollutants in contaminated soils and have attracted significant attention. Chinese coke production making a great contribution to the globe is increasingly identified as the non-ignorable source of EPFRs. However, the distribution level, influence factors, and biotoxicity of EPFRs at coking sites remain poorly understood. Herein, a typical coking plant in Tangshan, China, featuring two functional regions (the reconstructed project (RP) and elimination engineering (EE)) was used to study the existence of EPFRs. The spin density of the EPFRs in coking soils was 3.20 × 1020-3.11 × 1021 spins/g with g-factor values of 2.0020-2.0036. The EPFRs presented higher concentrations and g-factor values in RP region than in EE region, and a mixture of carbon-centered radicals and carbon-centered radicals with adjacent oxygen atoms as well as carbon-centered radical was ascertained in the former and the latter, respectively. Correlation analysis and FT-ICR-MS results indicated that polycyclic aromatic hydrocarbons (PAH) together with other unsaturated hydrocarbons and condensed aromatic contaminants, might contribute to the EPFRs formation in the soils of RP region, whereas PAHs were the main source of EPFRs in EE region. Soil components were determined to investigate the influence factors in EPFRs formation. Cu and Fe2O3 were recognized as the markedly positive influence factors, while TOC had a negative impact on EPFR formation. Visible light irradiation can induce the transformation and generation of EPFRs. As representative contaminants, both toluene and 2-chlorophenol can create EPFRs in coking soil under visible light irradiation. The potential biotoxicity tests of Photobacterium phosphoreum T3 spp. showed that EPFRs from the soils diminished bacterial luminescence. Such effect was proven to be induced by the OH based on the quenching experiment. Understanding the influence factors of EPFRs formation and their biotoxicity in coking soils is critical for developing risk assessments and prevention strategies.