Germacrone alleviates breast cancer-associated osteolysis by inhibiting osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways.

Bone is one of the most frequent sites for metastasis in breast cancer patients. Bone metastasis significantly reduces the survival time and the life quality of breast cancer patients. Germacrone (GM) can serve humans as an anti-cancer and anti-inflammation agent, but its effect on breast cancer-induced osteolysis remains unclear. This study aims to investigate the functions and mechanisms of GM in alleviating breast cancer-induced osteolysis. The effects of GM on osteoclast differentiation, bone resorption, F-actin ring formation, and gene expression were examined in vitro. RNA-sequencing and Western Blot were conducted to explore the regulatory mechanisms of GM on osteoclastogenesis. The effects of GM on breast cancer-induced osteoclastogenesis, and breast cancer cell malignant behaviors were also evaluated. The in vivo efficacy of GM in the ovariectomy model and breast cancer bone metastasis model with micro-CT and histomorphometry. GM inhibited osteoclastogenesis, bone resorption and F-actin ring formation in vitro. Meanwhile, GM inhibited the expression of osteoclast-related genes. RNA-seq analysis and Western Blot confirmed that GM inhibited osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways. The in vivo mouse osteoporosis model further confirmed that GM inhibited osteolysis. In addition, GM suppressed the capability of proliferation, migration, and invasion and promoted the apoptosis of MDA-MB-231 cells. Furthermore, GM could inhibit MDA-MB-231 cell-induced osteoclastogenesis in vitro and alleviate breast cancer-associated osteolysis in vivo human MDA-MB-231 breast cancer bone metastasis-bearing mouse models. Our findings identify that GM can be a promising therapeutic agent for patients with breast cancer osteolytic bone metastasis.

Spatial distribution characteristics and degradation mechanism of microorganisms in n-hexadecane contaminated vadose zone.

The damage caused by petroleum hydrocarbon pollution to soil and groundwater environment is becoming increasingly significant. The vadose zone is the only way for petroleum hydrocarbon pollutants to leak from surface into groundwater. The spatial distribution characteristics of indigenous microorganisms in vadose zone, considering presence of capillary zones, have rarely been reported. To explore the spatial distribution characteristics of indigenous microorganisms in vadose zone contaminated by petroleum hydrocarbons, a one-dimensional column migration experiment was conducted using n-hexadecane as characteristic pollutant. Soil samples were collected periodically from different heights during experiment. Corresponding environmental factors were monitored online. The microbial community structure and spatial distribution characteristics of the cumulative relative abundance were systematically analyzed using 16S rRNA sequencing. In addition, the microbial degradation mechanism of n-hexadecane was analyzed using metabolomics. The results showed that presence of capillary zone had a strong retarding effect on n-hexadecane infiltration. Leaked pollutants were mainly concentrated in areas with strong capillary action. Infiltration and displacement of NAPL-phase pollutants were major driving force for change in moisture content (θ) and electric conductivity (EC) in vadose zone. The degradation by microorganisms results in a downward trend in potential of hydrogen (pH) and oxidation-reduction potential (ORP). Five petroleum hydrocarbon-degrading bacterial phyla and 11 degradable straight-chain alkane bacterial genera were detected. Microbial degradation was strong in the area near edge of capillary zone and locations of pollutant accumulation. Mainly Sphingomonas and Nocardioides bacteria were involved in microbial degradation of n-hexadecane. Single-end oxidation involved microbial degradation of n-hexadecane (C16H34). The oxygen consumed, hexadecanoic acid (C16H32O2) produced during this process, and release of hydrogen ions (H+) were the driving factors for reduction of ORP and pH. The vadose zone in this study considered presence of capillary zone, which was more in line with actual contaminated site conditions compared with previous studies. This study systematically elucidated vertical distribution characteristics of petroleum hydrocarbon pollutants and spatiotemporal variation characteristics of indigenous microorganisms in vadose zone considered presence of capillary zone. In addition, the n-hexadecane degradation mechanism was elucidated using metabolomics. This study provides theoretical support for development of natural attenuation remediation measures for petroleum-hydrocarbon-contaminated soil and groundwater.

Study on medicinal food plants in the Gaoligongshan Biosphere Reserve, the richest biocultural diversity center in China.

BACKGROUND: Traditional knowledge associated with medicinal food plants (MFPs) plays a vital role in fighting hidden hunger and safeguarding the health of local people. MFPs resources are abundant in the Gaoligongshan area, a biosphere reserve with the richest biocultural diversity in China. Local people of different linguistic groups also have rich traditional botanical knowledge. However, there are still few comprehensive and systematic studies on MFPs there. METHODS: Ethnobotanical investigation including market survey, semi-structured interviews, free listing and key informant interviews was conducted in the Gaoligongshan area, Western Yunnan, Southwest China. A total of 13 local farmers' markets were selected and information about medicinal food plants, including food categories, medicinal and edible parts, modes of consumption, medicinal effects, and distribution were collected. The relative occurrence frequency (RFO) and cultural food significance index (CFSI) were calculated to identify the culturally significant MFPs. RESULTS: A total of 184 species of MFPs, belonging to 83 families, were collected in the Gaoligongshan area, including vegetables (77), medicinal diets (26), fruits (25), spices (18), herbal tea (13), tea substitutes (11), substitutes for staple food (8), nuts (5), oils and fats (4), and dye material (1). The most frequently used families were Fabaceae, Asteraceae and Apiaceae, with 11, 10, and 9 species, respectively. The most frequently used plant parts were the stems, followed by fruits and leaves. Based on the evaluation results of the CFSI and RFO indices, 18 species of MFPs with magnificent local cultural importance have been screened out, such as Houttuynia cordata, Eryngium foetidum, Sechium edule, Centella asiatica and Pseudocydonia sinensis. CONCLUSION: These findings have guiding significance for conservation of traditional knowledge associated with MFPs and facilitation of scientific utilization of MFPs to meet local people's needs for a healthy life.

Phytic Acid-Promoted Exfoliation of Black Phosphorus Nanosheets for the Fabrication of Photothermal Antibacterial Coatings.

Medical device-associated infections (MDAI) caused by planktonic pathogens are of serious concern worldwide due to the emergence of drug resistance resulting from continuous overuse or misuse of antibiotics. Therefore, the design of non-antibiotics-based treatment for MDAI is of crucial importance. Black phosphorus (BP), a novel 2D material, has recently received much attention owing to its remarkable physical, chemical, mechanical, and functional features. However, the intricacy of the fabrication process has severely hampered the development of BP in prospective applications. In this study, a simple and eco-friendly liquid-phase exfoliation method of phytic acid (PA)-promoted exfoliation of BP nanosheets (PA@BP NSs) is developed for their potential application in antibacterial photothermal therapy. To impart the antimicrobial effects, the polydimethylsiloxane surfaces are functionalized with quaternized polymer (polyquaternium-2 or PQ) and PA@BP NSs, leading to the formation of PA-BP-PQ composite coatings. In addition to the contact-killing antibacterial effect of the cationic PQ, the PA-BP-PQ coating exhibits remarkable near-infrared irradiation-triggered bactericidal effects with low cytotoxicity both in vitro and in vivo. This study proposes a simple liquid-phase exfoliation technique for the fabrication of BP NSs and a one-step approach for the construction of PA-BP-PQ composite coatings for bi-modal (contact-killing and photothermal) antimicrobial therapy.

Effect of a Baduanjin intervention on the risk of falls in the elderly individuals with mild cognitive impairment: a study protocol for a randomized controlled trial.

BACKGROUND: Falls are a global public problem and may be an important cause of death in older adults. However, older adults with mild cognitive impairment(MCI) are more likely to fall and suffer more damage than older adults with normal cognitive function, which shows the importance of preventing falls. More and more evidence shows that Baduanjin can improve the balance function of the elderly and reduce the risk of falls in the elderly with MCI, but the mechanism is still unclear. The main purpose of this study is to verify the intervention effect of Baduanjin training on the risk of falls in elderly people with MCI and to elucidate the underlying mechanism of Baduanjin training in reducing the risk of falls in MCI patients. METHODS: In this prospective study, outcome assessor-blind, three-arm randomized controlled trial, a total of 72 eligible participants will be randomly allocated (1:1:1) into the 12-week Baduanjin exercise intervention (60 min per session, three sessions per week), the 12-week brisk walking group(60 min per session, three sessions per week) or the 12-week health education group. Primary outcome is the Fall-Risk Self-Assessment Questionnaire(FRQ), and secondary outcomes are fall efficacy index, gait assessment, balance function, lower limb muscle strength, cognitive function, activities of daily living(ADL) and MRI scans. In addition to the MRI scans, which will be measured before and after the intervention,other primary and secondary outcomes will be assessed at baseline, 6 weeks, and 12 weeks (at the end of the intervention) and after an additional 12-week follow-up period. The mixed linear model will be conducted to observe the intervention effects. DISCUSSION: This trial will investigate the effect of Baduanjin exercise on the prevention of falls in elderly individuals with MCI, explore the imaging mechanism of Baduanjin exercise to reduce the risk of falls in elderly individuals with MCI from the perspective of vestibular neural network, and provide strong evidence for Baduanjin exercise to reduce the risk of falls in elderly individuals with MCI, as well as provide new ideas and approaches for the central mechanism of Traditional Chinese Medicine(TRC) rehabilitation methods to intervene in falls in elderly. TRIAL REGISTRATION: Chictr.org.cn, ID: ChiCTR2200057520. Registered on 14 March 2022, https://www.chictr.org.cn/showproj.html?proj=146592 .

Effect of high-frequency repetitive transcranial magnetic stimulation under different intensities upon rehabilitation of chronic pelvic pain syndrome: protocol for a randomized controlled trial.

INTRODUCTION: Nearly one in seven women worldwide suffers from chronic pelvic pain syndrome (CPPS) each year. Often, CPPS necessitates a combination of treatments. Studies have shown the good therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) upon CPPS. We wish to undertake a randomized controlled trial (RCT) to observe the effect of high-frequency rTMS at different intensities upon CPPS. METHODS AND ANALYSES: In this prospective, double-blinded RCT, 63 female CPPS participants will be recruited and randomized (1:1:1) to high-intensity rTMS, low-intensity rTMS, or sham rTMS. The control group will receive a 10-day course of conventional pelvic floor (PF) rehabilitation (neuromuscular stimulation, magnetic therapy, or light therapy of the PF). On the basis of conventional treatment, participants in the high-intensity rTMS group will receive pulses of 10 Hz with a resting motor threshold (RMT) of 110% for a total of 15,000 pulses. Participants in the low-intensity rTMS group will receive pulses of 10 Hz with an RMT of 80% with 15,000 pulses. The sham rTMS group will be subjected to sham stimulation with the same sound as produced by the real magnetic stimulation coil. The primary outcome will be determined using a visual analog scale, the Genitourinary Pain Index, Zung Self-Rating Anxiety Scale, and Zung Self-Rating Depression Scale. The secondary outcome will be determined by electromyography of the surface of PF muscles at baseline and after treatment completion. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of Bao'an People's Hospital, Shenzhen, Guangdong Province (approval number: BYL20211203). The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences (Protocol version 1.0-20220709). TRIAL REGISTRATION: Chictr.org.cn, ID: ChiCTR2200055615. Registered on 14 January 2022, http://www.chictr.org.cn/showproj.aspx?proj=146720 . Protocol version 1.0-20220709.

Association between glucosamine use and cancer mortality: A large prospective cohort study.

Objective: Previous studies have shown anti-cancer and anti-inflammatory benefits of glucosamine. This study was performed to prospectively evaluate the association between glucosamine supplementation and the mortality of multiple cancers based on the UK Biobank cohort study. Materials and methods: A total of 453,645 participants aged 38-73 who had no cancer at baseline were recruited between 2006 and 2010 and followed until March 2021. We used cox and poission proportional hazards models to explore the association between habitual use of glucosamine and cancer mortality. Subgroup analyses were conducted to understand the potential effect modifications of demographics, lifestyle factors, and health outcomes. Sensitivity analyses were performed to determine the robustness of the results. Results: Of the participants, 88,224 (19.4%) reported habitual glucosamine use at baseline. There were 9,366 cancer deaths during a median follow-up of 12.1 years, and we observed a significant association between the use of glucosamine and lower overall cancer mortality (HR = 0.95, 95% CI = 0.90-1.00, p < 0.05), kidney cancer (IRR = 0.68, 95% CI = 0.49-0.95, p < 0.05), lung cancer mortality (IRR = 0.84, 95% CI = 0.74-0.95, p < 0.05), and rectum cancer (IRR = 0.76, 95% CI = 0.59-0.98, p < 0.05). Subgroup analysis showed that habitual glucosamine supplementation was correlated with lower overall cancer mortality among participants who were aged ≥ 60 years, male, current smoker, without high cholesterol and not obese. Sensitivity analysis showed that the results were stable. Conclusion: Habitual glucosamine use was significantly related to decreased overall cancer, kidney cancer, lung cancer, and rectum cancer mortality, based on data from the large-scale, nationwide, prospective UK Biobank cohort study.

Microwave-induced steam distillation (MISD) remediation in petroleum hydrocarbon-contaminated sites: From process improvement to pilot application.

The process improvement, a pilot remediation test and the decontamination mechanism of microwave-induced steam distillation (MISD) for petroleum hydrocarbons (PHs) removal were conducted. Processes of multistage steam distillation and carbon reinforcement were compared to determine the best remediation process. Pilot project was then carried out to explore the applicability of MISD in site-scale remediation. The remediation efficiency, procedures and influencing factors of site-scale MISD project were studied by monitoring variations of soil moisture, temperature and PHs concentrations. Furthermore, the decontamination mechanisms of PHs were clarified based on kinetic analysis. The results showed that the multistage steam distillation could improve 10%∼15% remediation efficiency, and the carbon reinforcement could shorten remediation duration of each steam distillation stage by 50%. Pilot MISD project adopted multistage steam distillation process and went through four (initial, rapid heating-up, gentle heating-up and quasi-equilibrium) remediation stages (overall temperature ≤100 °C). The final PHs removal rate was about 60%, which would get better with greater proportion of low boiling points components and stronger vapor extraction. Kinetic studies showed that PHs was removed by steam stripping and limited by intraparticle diffusion in the "steam distillation zone", while local high temperature (＞100 °C) greatly improved PHs volatilization and provided activation energy for PHs desorbed and degraded in the "selective heating zone".

Nitrate and nitrite pathways and dynamic changes in bacterial communities during beet sugar processing.

BACKGROUND: Bacterial community successions were surveyed during the processing stages of sugar production using high-throughput sequencing methods. Furthermore, the correlation between bacterial community and nitrate/nitrite content in beet sugar processing were investigated. RESULTS: In an analysis of the V3-V4 region of the 16S rDNA gene, 254 122 effective sequences were obtained from samples, which included sugar beet, cossettes, diffusion juice, second-phase diffusion juice, light juice and thick juice. The results showed that dominant genera included Pantoea, Pseudomonas, Leuconostoc and Burkholderia. Moreover, significant changes in bacterial communities were observed in samples. Regarding the relevant nitrogen metabolic potential, this study revealed communities with the ability for nitrate and nitrite metabolism. Furthermore, a shaking experiment involving diffusion juice and second-phase diffusion juice was performed, and results showed that the nitrate level declined 73% and 98% in 36 h, respectively. These results suggested that the bacterial communities contribute to nitrate and nitrite transformation. CONCLUSION: This study illustrated that the bacterial communities and their specific effects on the formation of nitrate and nitrite during beet sugar processing. The results presented the basic concept involving the nitrate- and nitrite-forming pathways directly related to the mechanism of bacterial community growth. This study could facilitate an understanding of the correlation between nitrite content and microorganisms to guide beet sugar manufacturers regarding the control of nitrite and nitrate content. © 2021 Society of Chemical Industry.