Effects of Drying Methods on the Physicochemical and Functional Properties of Cinnamomum camphora Seed Kernel Protein Isolate.

Cinnamomum camphora seed kernel protein isolate (CPI) has attracted increasing attention due to its sustainability and potential applications. This study aimed to investigate the effects of freeze-drying (FD), vacuum-drying (VD), and spray-drying (SD) on the physicochemical and functional properties of CPI. The morphology observation results showed that the SD-CPI, SD-CPI, and VD-CPI were spherical, lamellar, and massive, respectively. Compared to FD and SD, VD had more impact on the color, surface hydrophobicity, intermolecular disulfide bonds, intrinsic fluorescence, and thermal stability of CPI. Fourier transform infrared spectroscopy (FTIR) analyses showed that among three CPI samples, VD-CPI had the highest content of ß-sheet but the lowest contents of α-helix and ß-turn. At different pH values, the solubility, emulsification, and foaming properties of VD-CPI were inferior to those of FD-CPI and SD-CPI. These results provide useful information on the changes in the physicochemical and functional properties of CPI subjected to different drying methods, and offer theoretical guidance for the production and use of CPI in the food industry.

Assessment of Heart Rate Monitoring During Exercise With Smart Wristbands and a Heart Rhythm Patch: Validation and Comparison Study.

BACKGROUND: The integration of wearable devices into fitness routines, particularly in military settings, necessitates a rigorous assessment of their accuracy. This study evaluates the precision of heart rate measurements by locally manufactured wristbands, increasingly used in military academies, to inform future device selection for military training activities. OBJECTIVE: This research aims to assess the reliability of heart rate monitoring in chest straps versus wearable wristbands. METHODS: Data on heart rate and acceleration were collected using the Q-Band Q-69 smart wristband (Mobile Action Technology Inc) and compared against the Zephyr Bioharness standard measuring device. The Lin concordance correlation coefficient, Pearson product moment correlation coefficient, and intraclass correlation coefficient were used for reliability analysis. RESULTS: Participants from a Northern Taiwanese medical school were enrolled (January 1-June 31, 2021). The Q-Band Q-69 demonstrated that the mean absolute percentage error (MAPE) of women was observed to be 13.35 (SD 13.47). Comparatively, men exhibited a lower MAPE of 8.54 (SD 10.49). The walking state MAPE was 7.79 for women and 10.65 for men. The wristband's accuracy generally remained below 10% MAPE in other activities. Pearson product moment correlation coefficient analysis indicated gender-based performance differences, with overall coefficients of 0.625 for women and 0.808 for men, varying across walking, running, and cooldown phases. CONCLUSIONS: This study highlights significant gender and activity-dependent variations in the accuracy of the MobileAction Q-Band Q-69 smart wristband. Reduced accuracy was notably observed during running. Occasional extreme errors point to the necessity of caution in relying on such devices for exercise monitoring. The findings emphasize the limitations and potential inaccuracies of wearable technology, especially in high-intensity physical activities.

Targeting the DNA repair pathway for breast cancer therapy: Beyond the molecular subtypes.

DNA repair is a vital mechanism in cells that protects against DNA damage caused by internal and external factors. It involves a network of signaling pathways that monitor and transmit damage signals, activating various cellular activities to repair DNA damage and maintain genomic integrity. Dysfunctions in this repair pathway are strongly associated with the development and progression of cancer. However, they also present an opportunity for targeted therapy in breast cancer. Extensive research has focused on developing inhibitors that play a crucial role in the signaling pathway of DNA repair, particularly due to the remarkable success of PARP1 inhibitors (PARPis) in treating breast cancer patients with BRCA1/2 mutations. In this review, we summarize the current research progress and clinical implementation of BRCA and BRCAness in targeted treatments for the DNA repair pathway. Additionally, we present advancements in diverse inhibitors of DNA repair, both as individual and combined approaches, for treating breast cancer. We also discuss the clinical application of DNA repair-targeted therapy for breast cancer, including the rationale, indications, and summarized clinical data for patients with different breast cancer subtypes. We assess their influence on cancer progression, survival rates, and major adverse reactions. Last, we anticipate forthcoming advancements in targeted therapy for cancer treatment and emphasize prospective areas of development.

Efficiency and ecological safety of herbicide haloxyfop-R-methyl on removal of coastal invasive plant Spartina alterniflora.

Spartina alterniflora is a global invasive plant and has caused considerable damage to coastal wetland ecosystem. This study evaluated the efficiency and ecological safety of herbicide haloxyfop-R-methyl (HPME) in removing S alterniflora in Laizhou Bay. The results showed that the density of regenerated S. alterniflora after 10 months of application of 0.01, 0.02 and 0.03 g/m2 HPME decreased by 86.67 %, 99.16 % and 99.31 %, respectively. Moreover, seed abortion rates were 62.25 %, 92.24 % and 94.82 %, and weight of roots in HPME groups were 56.63 %, 59.99 %, and 40.10 % of those in the control group. After 4 days of application, HPME could not be detected in S. alterniflora and sediments. In addition, HPME did not change sediment physicochemical properties, macrozoobenthos community and microbial community structure during 16 days, but increased the density of native macrozoobenthos after 1 year. Therefore, HPME might be an effective and ecologically safe chemical for the eradication of S. alterniflora.

A fast chemical reprogramming system promotes cell identity transition through a diapause-like state.

Cellular reprogramming by only small molecules holds enormous potentials for regenerative medicine. However, chemical reprogramming remains a slow process and labour intensive, hindering its broad applications and the investigation of underlying molecular mechanisms. Here, through screening of over 21,000 conditions, we develop a fast chemical reprogramming (FCR) system, which significantly improves the kinetics of cell identity rewiring. We find that FCR rapidly goes through an interesting route for pluripotent reprogramming, uniquely transitioning through a developmentally diapause-like state. Furthermore, FCR critically enables comprehensive characterizations using multi-omics technologies, and has revealed unexpected important features including key regulatory factors and epigenetic dynamics. Particularly, activation of pluripotency-related endogenous retroviruses via inhibition of heterochromatin significantly enhances reprogramming. Our studies provide critical insights into how only environmental cues are sufficient to rapidly reinstate pluripotency in somatic cells, and make notable technical and conceptual advances for solving the puzzle of regeneration.

Small cytosolic double-stranded DNA represses cyclic GMP-AMP synthase activation and induces autophagy.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.

L-Arginine-Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function.

Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L-arginine-loaded selenium-coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)-induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI.

Erratum: Dual-Targeted Gold Nanoprism for Recognition of Early Apoptosis, Dual-Model Imaging and Precise Cancer Photothermal Therapy: Erratum.

[This corrects the article DOI: 10.7150/thno.34755.].

Caseworker Cultural Mediator Involvement in Neurocritical Care for Patients and Families With Non-English Language Preference: A Quality Improvement Project.

Objective To describe Harborview Medical Center's experience with the involvement of caseworker cultural mediators (CCM) for patients requiring neurocritical care. Methods Using univariate and multivariate analysis (model adjusted for age, Glasgow Coma Scale score (GCS), Sequential Organ Failure Assessment (SOFA) Scores, mechanical ventilation, transition to comfort measures only (CMO), and death by neurologic criteria), we examined CCM team members' involvement in the care of Amharic/Cambodian/Khmer/Somali/Spanish/Vietnamese patients admitted to our neurocritical care service between 2014-2022, factors associated with CCM utilization, and changes in CCM utilization after a QI initiative was implemented in 2020 to encourage healthcare providers to consult the CCM team. Results Compared to eligible patients (n=827) who did not receive CCM referral, patients with CCM involvement (n=121) were younger (49 [interquartile range, IQR 38,63] vs. 56 [IQR 42,68] years, p = 0.002), had greater illness severity (admission GCS 8.5 [IQR 3,14] vs. 14 [IQR 7,15], p < 0.001, SOFA scores (5 [IQR 2,8] vs. 4 [IQR2,6], p = 0.007), and more frequently required mechanical ventilation (67% vs. 40%, odds ratio, OR 3.07, 95% CI 2.06,4.64), with higher all-cause mortality (20% vs. 12%, RR 1.83, 95% CI 1.09, 2.95), and with a higher rate of transition to CMO (11.6% vs. 6.2%, OR 2.00, 95% CI 1.03;3.66). The CCM QI initiative was independently associated with increased CCM involvement (aOR 4.22, 95% CI [2.32;7.66]). Overall, 4/10 attempts made by CCMs to reach out to the family to provide support were declined by the family. CCMs reported providing cultural/emotional support (n=96, 79%), end-of-life counseling (n=16, 13%), conflict mediation (n=15, 12.4%), and facilitating goals of care meetings (n=4, 3.3%). Conclusions Among eligible patients, CCM consultations appeared to occur in patients with higher disease severity. Our QI initiative increased CCM involvement.

Light-triggered photosynthetic engineered bacteria for enhanced-photodynamic therapy by relieving tumor hypoxic microenvironment.

Background: Singlet oxygen (1O2) has received considerable research attention in photodynamic therapy (PDT) due to its cytotoxic solid features. However, the inherent hypoxic state of the tumor microenvironment (TME) leads to the meager 1O2 quantum yield of inorganic PDT reagents, and their application in vivo remains elusive. Methods: We developed a novel strategy to fabricate active photosynthetic bacteria/photosensitizer/photothermal agent hybrids for photosynthetic tumor oxygenation and PDT and PTT tumor therapy under different laser irradiation sources. Photosynthetic bacteria combined with Ce6 photosensitizer and Au NPs photothermal agent, the obtained Bac@Au-Ce6 effectively targets tumor tissues and further enhances the tumor accumulation of Au-Ce6. Results: The results showed that the Au-Ce6-loaded engineered bacteria (Bac@Au-Ce6) maintained the photosynthetic properties of Syne. After i.v. injection, Bac@Au-Ce6 efficiently aggregates at tumor sites due to the tumor-targeting ability of active Syne. With 660 nm laser irradiation at the tumor site, the photoautotrophic Syne undergoes sustained photosynthetic O2 release and immediately activates O2 to 1O2 via a loaded photosensitizer. PTT was subsequently imparted by 808 laser irradiations to enhance tumor killing further. Conclusions: This work provides a new platform for engineering bacteria-mediated photosynthesis to promote PDT combined with PTT multi-faceted anti-tumor.

Analysis on the properties of hydrolyzed amino acids in typical municipal sludge.

In this study, amino acids, proteins, and microbial communities in sludge from different wastewater treatment plants (WWTPs) were analyzed. The results showed that the bacterial communities of different sludge samples were similar at the phylum level, and the dominant bacterial species in sludge samples with the same treatment process were the consistent. The main amino acids in EPS of different layers were different, and the amino acid results of different sludge samples were quite different, but the content of hydrophilic amino acids in all samples was higher than that of hydrophobic amino acids. And the total content of glycine, serine, and threonine related to sludge dewatering was positively correlated with protein content in sludge. In addition, the content of nitrifying bacteria and denitrifying bacteria in sludge was also positively correlated with the content of hydrophilic amino acids. In this study, the correlations between proteins, amino acids, and microbial communities in sludge were analyzed respectively, and the internal relationship was found. And it provided ideas for further study of sludge dewatering characteristics in the future.

Regeneration of articular cartilage defects: Therapeutic strategies and perspectives.

Articular cartilage (AC), a bone-to-bone protective device made of up to 80% water and populated by only one cell type (i.e. chondrocyte), has limited capacity for regeneration and self-repair after being damaged because of its low cell density, alymphatic and avascular nature. Resulting repair of cartilage defects, such as osteoarthritis (OA), is highly challenging in clinical treatment. Fortunately, the development of tissue engineering provides a promising method for growing cells in cartilage regeneration and repair by using hydrogels or the porous scaffolds. In this paper, we review the therapeutic strategies for AC defects, including current treatment methods, engineering/regenerative strategies, recent advances in biomaterials, and present emphasize on the perspectives of gene regulation and therapy of noncoding RNAs (ncRNAs), such as circular RNA (circRNA) and microRNA (miRNA).

Sex differences in risk factors for metabolic syndrome in middle-aged and senior hospital employees: a population-based cohort study.

BACKGROUND: Several cross-sectional studies have reported risk factors for metabolic syndrome (MetS). However, these studies did not focus on sex differences in middle-aged and senior populations or employ a longitudinal design. These study design differences are important, as there are sex differences in lifestyle habits associated with MetS, and middle-aged and senior individuals have increased MetS susceptibility. Therefore, the purpose of this study was to examine whether sex differences influenced MetS risk over a ten-year follow-up period among middle-aged and senior hospital employees. METHODS: This population-based and prospective cohort study enrolled 565 participants who did not have MetS in 2012 for a ten-year repeated-measurement analysis. Data were retrieved from the hospital's Health Management Information System. Analyses included Student's t tests, χ2 tests and Cox regression. P < 0.05 indicated statistical significance. RESULTS: Male middle-aged and senior hospital employees had an elevated MetS risk (hazard ratio (HR) = 1.936, p < 0.001). Men with more than four family history risk factors had an increased risk of MetS (HR = 1.969, p = 0.010). Women who worked shift duty (HR = 1.326, p = 0.020), had more than two chronic diseases (HR = 1.513, p = 0.012), had three family history risk factors (HR = 1.623, p = 0.010), or chewed betel nuts (HR = 9.710, p = 0.002) had an increased risk of MetS. CONCLUSIONS: The longitudinal design of our study improves the understanding of sex differences in MetS risk factors in middle-aged and senior adults. A significantly elevated risk of MetS over the ten-year follow-up period was associated with male sex, shift work, the number of chronic diseases, the number of family history risk factors, and betel nut chewing. Women who chewed betel nuts had an especially increased risk of MetS. Our study indicates that population-specific studies are important for the identification of subgroups susceptible to MetS and for the implementation of hospital-based strategies.

Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic osteoarthropathy characterized by the progressive degeneration of articular cartilage and synovial inflammation. Early OA clinical treatments involve intra-articular injection of glucocorticoids, oral acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), which are used for anti-inflammation and pain relief. However, long-term use of these agents will lead to inevitable side effects, even aggravate cartilage loss. At present, there are no disease-modifying OA drugs (DMOADs) yet approved by regulatory agencies. Polarization regulation of synovial macrophages is a new target for OA treatment. Inhibiting M1 polarization and promoting M2 polarization of synovial macrophages can alleviate synovial inflammation, relieve joint pain and inhibit articular cartilage degradation, which is a promising strategy for OA treatment. In this study, we describe the molecular mechanisms of macrophage polarization and its key role in the development of OA. Subsequently, we summarize the latest progress of strategies for OA treatment through macrophage reprogramming, including small molecule compounds (conventional western medicine and synthetic compounds, monomer compounds of traditional Chinese medicine), biomacromolecules, metal/metal oxides, cells, and cell derivatives, and interprets the molecular mechanisms, hoping to provide some information for DMOADs development.

Live bio-nano-sonosensitizer targets malignant tumors in synergistic therapy.

Sonosensitizers that can increase the concentration of reactive oxygen species (ROS) within a tumor microenvironment is a high priority for sonodynamic therapy (SDT). In this study, a functionalized, smart nanosonosensitizer based on Au-RuO2 nanoparticles (NPs) and selenium nanoparticles (Se NPs) that were electrostatically self-assembled onto the surface of Listeria innocua (LI) was used to create Bac@ARS. Au NPs provided the core in which RuO2 was deposited to form Au-RuO2 NPs. Additionally, the underlying properties of the Au NPs and Se NPs were used to optimize the sonosensitivity performance. Compared with pristine RuO2 NPs, Bac@ARS exhibits highly efficient ROS-producing activity. Furthermore, Bac@ARS remodeled the hypoxic tumor microenvironment, enabling overproduction of ROS. Importantly, Bac@ARS exploits the natural tropism of LI to selectively accumulate in tumors, which improved the treatment precision at hypoxic tumor sites after sonodynamic activation. However, the activity of LI was greatly reduced after ultrasound (US) irradiation, ensuring the biosafety of Bac@ARS. Bac@ARS was also used to monitor tumors, in real time, using photoacoustic imaging of the gold-based nanoparticles. Therefore, Bac@ARS is a promising microbial sonosensitizer providing a new platform for the optimization of sonosensitizers for tumor treatment. STATEMENT OF SIGNIFICANCE: A bio-nano-sonosensitizer was designed using a Au nanoparticle (NP) core modified with RuO2 NPs. The Au-RuO2 NPs together with Se-NPs are attached via electrostatic adsorption to a live bacterium Listeria innocua (LI), creating Bac@ARS. The role of the NPs was to optimize the sonosensitivity performance at the target tumor site. Bac@ARS reshaped the tumor microenvironment and overcame tumor hypoxia leading to ROS overproduction. This activated a potent ICD-mediated cellular immunity and anti-tumor activity. Importantly, Bac@ARS exploited the natural tropism of LI to selectively accumulate in tumors, resulting in more precise delivery of the therapeutic effect while exhibiting reduced effects on healthy tissues.

The leucine-responsive regulatory protein SCAB_Lrp modulates thaxtomin biosynthesis, pathogenicity, and morphological development in Streptomyces scabies.

Streptomyces scabies is the best-characterized plant-pathogenic streptomycete, which is a special species among the large genus Streptomyces. The pathogenicity of S. scabies relies on the production of the secondary metabolite thaxtomin A. Little is known about the molecular mechanisms underlying the regulation of thaxtomin biosynthesis in S. scabies beyond the pathway-specific activator TxtR and the cellulose utilization repressor CebR. The leucine-responsive regulatory protein (Lrp) family modulates secondary metabolism in nonpathogenic streptomycetes. However, the regulatory relationship between the Lrp and pathogenic streptomycetes remains unknown. In this study, we demonstrated that SCAB_Lrp (SCAB_77931) from S. scabies significantly affects thaxtomin biosynthesis, pathogenicity, and morphological development. SCAB_Lrp deletion resulted in a dramatic decline in thaxtomin A production and a low-virulence phenotype of S. scabies. An in-depth dissection of the regulatory mechanism of SCAB_Lrp revealed that it positively regulates the transcription of the thaxtomin biosynthetic gene cluster by directly binding to the promoter of the cluster-situated regulator gene txtR. SCAB_Lrp also controls the morphological development of S. scabies by directly activating the transcription of amfC, whiB, and ssgB. SCAB_Lrp directly controls the transcription of its own gene by binding a specific sequence (5'-GGACAGTCGCCGTGCTACG-3'). Moreover, phenylalanine and methionine have been characterized as SCAB_Lrp effectors by strengthening the binding affinity and complex status between SCAB_Lrp and DNA. Our findings characterize a multifunctional regulatory protein, SCAB_Lrp, that controls secondary metabolism, pathogenicity, and sporulation in S. scabies and provide new insights into the complex regulatory network that modulates thaxtomin phytotoxins in pathogenic Streptomyces.

Assessment of heavy metals contamination and human health risk assessment of the commonly consumed medicinal herbs in China.

This study investigates heavy metal contamination of commonly consumed medicinal herbs and human health risks to the Chinese population arising from the consumption of herbs that contain potentially harmful elements. Food safety standards for Chinese residents are becoming stricter, and much work in this field needs to be performed. This study examines Co, Ba, Fe, Cr, Mn, Ni, Zn, As, Cd, Pb, Cu, Be, Sb, and Bi concentrations in four regularly consumed Chinese herb species: Radix Paeoniae Alba (RPA), Radix Angelicae Dahuricae (RAD), Rhizoma Atractylodis Macrocephalae (RAM), and Radix Puerariae (RP). A pollution status examination and evaluation of heavy metals in RPA, RAD, RAM, and RP were performed. The human health risk assessment associated with the intake of potentially harmful elements in herbs was calculated in terms of the estimated daily intake (EDI), the target hazard quotient (THQ), the estimated hazard index (HI), and the lifetime cancer risk (CR). The mean single-factor pollution index (PI) showed that in the RPA, RAD, RAM, and RP samples, approximately 10.0%, 10.0%, 30.0%, and 10.0%, respectively, were polluted by Cd. The present study indicated that the pattern of consumption of the studied herbs in China does not seem to suggest an excessive health hazard associated with any of the toxic elements studied.

Multiple responses optimization of antioxidative components extracted from Fenugreek seeds using response surface methodology to identify their chemical compositions.

Fenugreek seeds (Trigonella foenum-graecum L.), one kind of traditional Chinese medicine, are reported to be of great potential as a new alternative in terms of their bioactive components. In our present study, an ultrasonic-assisted method was applied in the extraction of antioxidative components from fenugreek seeds. Four factors: ethanol concentration, liquid-solid ratio, sonication time, and sonication power were selected and multiple responses were studied using the response surface methodology (RSM). The effects of factors along with the correlation between all responses (flavonoids content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, OH- assay) were studied. The regression model indicated that all four factors are of significant effect on all responses. The model predicted that the ethanol concentration of 72%, solvent-to-material ratio of 35 ml/g, ultrasonic time of 41 min, and 500 W of power would provide a flavonoid yield of 9.10 mg/g, DPPH clearance of 80.33%, and OH- clearance of 24.28%, respectively. The confirmation test showed the closeness of the predicted results with those of experimental values. And AB-8 resin was successfully used to purify the fenuellus hulusi seed extract, and the flavonoid concentration of 78.14% was obtained. Six flavonoids (Swertisin, Puerarin apioside, Jasminoside B, Astragalin, Apigenin-7-O-beta-D-glucoside, and Apiin) were successfully identified by the liquid chromatography-mass spectrometry (LC-MS) analysis.