Sex-specific scaling of leaf phosphorus vs. nitrogen under unequal reproductive requirements in Eurya japonica, a dioecious plant.

PREMISE: Previous work searching for sexual dimorphism has largely relied on the comparison of trait mean vectors between sexes in dioecious plants. Whether trait scaling (i.e., the ratio of proportional changes in covarying traits) differs between sexes, along with its functional significance, remains unclear. METHODS: We measured 10 vegetative traits pertaining to carbon, water, and nutrient economics across 337 individuals (157 males and 180 females) of the diocious species Eurya japonica during the fruiting season in eastern China. Piecewise structural equation modeling was employed to reveal the scaling relationships of multiple interacting traits, and multivariate analysis of (co)variance was conducted to test for intersexual differences. RESULTS: There was no sexual dimorphism in terms of trait mean vectors across the 10 vegetative traits in E. japonica. Moreover, most relationships for covarying trait pairs (17 out of 19) exhibited common scaling slopes between sexes. However, the scaling slopes for leaf phosphorus (P) vs. nitrogen (N) differed between sexes, with 5.6- and 3.0-fold increases of P coinciding with a 10-fold increase of N in male and female plants, respectively. CONCLUSIONS: The lower ratio of proportional changes in P vs. N for females likely reflects stronger P limitation for their vegetative growth, as they require greater P investments in fruiting. Therefore, P vs. N scaling can be a key avenue allowing for sex-specific strategic optimization under unequal reproductive requirements. This study uncovers a hidden aspect of secondary sex character in dioecious plants, and highlights the use of trait scaling to understand sex-defined economic strategies.

[Morphological study of sexual reproductive disorders in Ligusticum chuanxiong].

Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.

Effect the accumulation of bioactive constituents of a medicinal plant (Salvia Miltiorrhiza Bge.) by arbuscular mycorrhizal fungi community.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with various terrestrial plants and have attracted considerable interest as biofertilizers for improving the quality and yield of medicinal plants. Despite the widespread distribution of AMFs in Salvia miltiorrhiza Bunge's roots, research on the impact of multiple AMFs on biomass and active ingredient accumulations has not been conducted. In this study, the effects of five native AMFs (Glomus formosanum, Septoglomus constrictum, Rhizophagus manihotis, Acaulospora laevis, and Ambispora gerdemannii) and twenty-six communities on the root biomass and active ingredient concentrations of S. miltiorrhiza were assessed using the total factor design method. RESULTS: Thirty-one treatment groups formed symbiotic relationships with S. miltiorrhiza based on the pot culture results, and the colonization rate ranged from 54.83% to 89.97%. AMF communities had higher colonization rates and total phenolic acid concentration than single AMF, and communities also appeared to have higher root fresh weight, dry weight, and total phenolic acid concentration than single inoculations. As AMF richness increased, there was a rising trend in root biomass and total tanshinone accumulations (ATTS), while total phenolic acid accumulations (ATP) showed a decreasing trend. This suggests that plant productivity was influenced by the AMF richness, with higher inoculation benefits observed when the communities contained three or four AMFs. Additionally, the affinities of AMF members were also connected to plant productivity. The inoculation effect of closely related AMFs within the same family, such as G. formosanum, S. constrictum, and R. manihotis, consistently yielded lower than that of mono-inoculation when any combinations were applied. The co-inoculation of S. miltiorrhiza with nearby or distant AMFs from two families, such as G. formosanum, R. manihotis, and Ac. laevis or Am. gerdemannii resulted in an increase of ATP and ATTS by more than 50%. AMF communities appear to be more beneficial to the yield of bioactive constituents than the single AMF, but overall community inoculation effects are related to the composition of AMFs and the relationship between members. CONCLUSION: This study reveals that the AMF community has great potential to improve the productivity and the accumulation of bioactive constituents in S. miltiorrhiza, indicating that it is an effective way to achieve sustainable agricultural development through using the AMF community.

Effect of cinnamon essential oil dietary supplementation on the growth, fatty acid composition, and meat quality of tilapia.

This study was conducted to investigate the effects of dietary supplementation of 0%, 0.2%, 0.35%, and 0.5% cinnamon essential oil on growth performance, fatty acid, and fillet quality of tilapia (Oreochromis niloticus). The results of growth experiments showed that the weight gain rate linearly and quadratically increased with increasing cinnamon essential oil doses (p < 0.05). The results of fatty acids experiments showed that the addition of essential oil significantly decreased the saturated fatty acids levels from 36.67% to 30.82% and increased the polyunsaturated fatty acids (PUFA) levels from 24.55% to 46.89%; especially, the n - 3 PUFA of 0.5% essential oil treatment showed the highest levels. Moreover, the n - 6 PUFA of 0.2% essential oil treatment were increased from 22.17% to 32.99%. The results of fillet quality experiments showed that the hardness and cohesiveness were linearly and quadratically increased with the increasing essential oil doses on days 4 and 7, respectively. The b* values linearly and quadratically decreased as the doses increased on day 7 (p < 0.05). The total volatile basic nitrogen levels were quadratically decreased with increasing cinnamon essential oil doses on day 7 (p < 0.05). In general, it can be concluded that cinnamon essential oil presented positive effects on the growth, nutritive values, and meat quality in tilapia.

Exploring the synergistic pharmacological mechanism of Huoxiang Drink against irritable bowel syndrome by integrated data mining and network pharmacology.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, characterized by abdominal pain, bloating, and changes in bowel habits. Huoxiang Drink (HD), derived from traditional Chinese medicine, has been reported to effectively treat digestive disorders caused by external cold and internal dampness. However, the pharmaceutical targets and mechanisms for HD against IBS remain unclear. Data mining, bioinformatics analysis, and network pharmacology were employed to explore the potential pharmacological mechanisms of HD against IBS. In this study, we screened 50 core targets to investigate the pharmacological mechanisms of HD against IBS. Enrichment analysis revealed that HD may participate in various signaling pathways, especially the inflammation-related tumor necrosis factor, signaling pathway and hypoxia-inducible factor signaling pathway. Molecular docking results confirmed that MOL000098 (Quercetin), MOL000006 (Luteolin), MOL005828 (Nobiletin), MOL005916 (Irisolidone), and MOL004328 (Naringenin), as key active ingredients in HD, bound to core targets (tumor protein P53, tumor necrosis factor, matrix metalloproteinases 9, and vascular endothelial growth factor-A) for topical treatment of IBS. This study suggested that HD offered a potential therapeutic strategy against IBS. Our findings may facilitate the efficient screening of active ingredients in HD and provide a theoretical basis for further validating the clinical therapeutic effects of HD on treating IBS.

Enhanced mechanical and functional properties of chitosan/polyvinyl alcohol/hydroxypropyl methylcellulose/alizarin composite film by incorporating cinnamon essential oil and tea polyphenols.

In this study, cinnamon essential oil and tea polyphenols were added to chitosan/ polyvinyl alcohol/ hydroxypropyl methylcellulose/ alizarin composite films to enhance their mechanical and functional properties. Their addition to the composite films enhanced their antibacterial and antioxidant properties and significantly improved its elongation at break (p < 0.05). Cinnamon essential oil reduced the water vapor permeability, water content, and water solubility of composite films and improved their transparency. The composite films with additive exhibited excellent UV-barrier ability and pH responsivity. Fourier Transform infrared spectroscopy and X-Ray Diffraction analyses confirmed hydrogen bond formation between the polymer molecules and additives. The results of Scanning Electron Microscope-Focused Ion Beam revealed improved surface and cross-section morphology of the films, leading to the generation of a cross-linked structure. Thermogravimetric and differential scanning calorimetry analysis indicated enhanced thermal stability of the composite films upon cinnamon essential oil addition. Analysis of storage quality indicators (TBARS value, TVC, and TVB-N) revealed that the composite films could prolong the freshness of surimi. The incorporation of cinnamon essential oil and tea polyphenols into the composite films has demonstrated significant potential as an effective and natural alternative for active food packaging.

Click-Reaction-Mediated Chemotherapy and Photothermal Therapy Synergistically Inhibit Breast Cancer in Mice.

The development of functional materials for tumor immunogenicity enhancement is desirable for overcoming the low therapeutic efficiency and easy metastasis during tumor treatments. Herein, the thermoresponsive nanoparticles composed of photothermal agent (PTA) and click reactive reagent are developed for enhanced immunotherapy application. A Ni-bis(dithiolene)-containing PTA with intense near-infrared absorption and efficient photothermal conversion is developed for thermoresponsive nanoparticles construction. The generated heat by encapsulated PTA further induces the phase transition of thermoresponsive nanoparticles with the release of chemotherapy reagent to react with the amino groups on functional proteins, realizing PTT and chemotherapy simultaneously. Moreover, the immunogenic cell death (ICD) of cancer cells evoked by PTT could be further enhanced by the released reactive reagent. As a result, the synergistic effect of photothermal treatment and reaction-mediated chemotherapy can suppress the growth of a primary tumor, and the evoked ICD could further activate the immune response with the suppression of a distant tumor. This synergistic treatment strategy provides a reliable and promising approach for cancer immunotherapy in clinic.

Daytime administration of melatonin has better protective effects on bone loss in ovariectomized rats.

OBJECTIVE: To explore the difference in the protective effects of intraperitoneal injection of exogenous melatonin of daytime or nighttime on bone loss in ovariectomized (OVX) rats. METHODS: After bilateral ovariectomy and sham surgery, 40 rats were randomly divided into four groups: sham operation group (Sham), ovariectomy (OVX), and daytime melatonin injection group (OVX + DMLT, 9:00, 30 mg/kg/d) and nighttime injection of melatonin (OVX + NMLT, 22:00, 30 mg/kg/d). After 12 weeks of treatment, the rats were sacrificed. The distal femur, blood and femoral marrow cavity contents were saved. The rest of the samples were tested by Micro-CT, histology, biomechanics and molecular biology. Blood was used for bone metabolism marker measurements. CCK-8, ROS, and Cell apoptosis are performed using MC3E3-T1 cells. RESULTS: Compared with treatment at night, the bone mass of the OVX rats was significantly increased after the daytime administration. All microscopic parameters of trabecular bone increased, only Tb.Sp decreased. Histologically, the bone microarchitecture of the OVX + DMLT was also more dense than the bone microarchitecture of the OVX + LMLT. In the biomechanical experiment, the femur samples of the day treatment group were able to withstand greater loads and deformation. In molecular biology experiments, bone formation-related molecules increased, while bone resorption-related molecules decreased. After treatment with melatonin administration at night, the expression of MT-1ß was significantly decreased. In cell experiments, the MC3E3-T1 cells treated with low-dose MLT had higher cell viability and greater efficiency in inhibiting ROS production than the MC3E3-T1 cells treated with high-dose MLT, which in turn more effectively inhibited apoptosis. CONCLUSION: Daytime administration of melatonin acquires better protective effects on bone loss than night in OVX rats.

[Traditional Chinese medicine therapy for rheumatoid arthritis: a review].

Rheumatoid arthritis(RA) is an autoimmune disease that seriously affects the physical and mental health of patients, but its pathogenesis is still unclear. At present, clinical treatment drugs include conventional synthetic disease modifing anti-rheumatic drugs(csDMARDs), nonsteroid anti-inflammtory drugs(NSAIDs), hormones, small molecule targeted drugs, biological agents, etc. These drugs can relieve the clinical symptoms of most patients with RA to a certain extent, but there are still many limitations, such as drug adverse reactions and individual differences in drug efficacy. Therefore, the research on drug treatment targets and the development of low-toxicity drugs helps further improve the precise prevention, diagnosis, and treatment of RA. There is an urgent need for efficient and low-toxic treatments to delay the clinical progress of RA. As a treasure of Chinese culture, traditional Chinese medicine(TCM) is widely used as an alternative therapy in the treatment of various diseases, and has a significant clinical efficacy. TCM therapy(including monomer traditional Chinese medicine, classical compounds, and non-drug therapies) has a significant curative effect on RA. Based on the literature research in recent years, this paper reviewed the clinical and mechanism research of TCM therapy in the treatment of RA, and provided more in-depth thinking for the wide application of TCM therapy in clinical practice.

Aloe polysaccharide promotes osteogenesis potential of adipose-derived stromal cells via BMP-2/Smads and prevents ovariectomized-induced osteoporosis.

BACKGROUND: Aloe polysaccharide (AP) is a type of an active macromolecule of Aloe vera, which contributes to its function. However, whether AP possesses anti-osteoporosis properties is unknown. METHODS: Adipose-derived stromal cells were treated with different concentrations of AP. Early and late osteogenesis were, respectively, evaluated by ALP and Alizarin Red S staining. The effect of AP on the processes of adipogenesis inhibition in ADSCs was analyzed by oil red O staining. Western blot was used to assess the expression of osteogenic and adipogenic related factors. Then, Noggin was administered to further confirm the mechanism by which AP promotes the osteogenesis of ADSCs. Finally, 40 female SD rats were classified into a bilateral laparotomy group (Sham group) and three bilateral ovariectomy groups: OVX group, OVX + AP group, and OVX + AP + Noggin group. The bilateral rat femurs were collected to perform micro-CT scanning, HE, Masson trichrome, and Oil red O staining. RESULTS: The results indicated that AP could increase ALP expression and calcium deposition. Through molecular mechanisms, AP promotes the protein expression of COL1A1, OPN, and ALP in ADSCs, but downregulates the expression of PPARγ. Also, AP directs ADSCs' fate by stimulating the BMP2/Smads signaling pathway. In vivo, the rat AP-treated had more trabecular bone than the OVX rat, indicating partial protection from cancellous bone loss after treatment with AP. CONCLUSION: Our results show that AP may promote osteogenesis of ADSCs through BMP-2/Smads signaling pathway and inhibits lipogenic differentiation. Thus, AP might be a promising alternative medicine to treat postmenopausal osteoporosis.

China rheumatoid arthritis registry of patients with Chinese medicine (CERTAIN): Rationale, design, and baseline characteristics of the first 11,764 enrollees.

BACKGROUND: Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA. PURPOSE: The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data. STUDY DESIGN: The CERTAIN is a prospective, multicenter, observational disease registry. METHODS: Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol. RESULTS: In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees. CONCLUSIONS: The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA. REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05219214).

Salvianolic acid A from Danhong Injection induces vasorelaxation by Regulating L-type calcium channel in isolated mouse arteries.

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI), which is a Chinese clinical prescription consists of Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese)(Plant names have been checked with http://www.theplantlist.org on March 1st, 2022), has been mainly used in the clinical therapy of cardiovascular diseases, including hypertension in China for many years. AIM OF THE STUDY: Cardiovascular diseases (CVDs) are the major causes of death all around the world. Due to the various stimulation, a series of vasoconstrictor substances are secreted to regulate the vasoconstriction function and then change blood pressure. The representative substances leading to abnormal vasoconstriction include renin-angiotensin system, endothelin, vasopressin and adrenaline, which act on the corresponding receptors on vascular smooth muscle to constrict blood vessels. Finally, blood pressure increases, followed by a series of cardiovascular diseases, including hypertension. However, little is known about Danhong injection's specific vasodilating mechanisms and active substances. The aims of the study were to determine the vasodilating substances of Danhong injection and explain its molecular mechanism of vasodilation. MATERIALS AND METHODS: The effects of DHI and its active components on vascular tension were measured by myograph system in the aortic or mesenteric rings of mice. Based on this, the pharmacodynamic substances were analyzed and effective molecules were found. Combined with multiple types of vascular myograph experiments and network pharmacological analysis, the molecular pathway was preliminarily determined. With molecular biology experiments, it was verified that the relevant mechanisms were closely related to calcium-mediated vasoconstriction in smooth muscle cells. RESULTS: DHI could relax endothelium-removed aortic rings pre-constricted with PE and 3 possible active vasodilator substances, including salvianolic acid A, salvianolic acid B and danshensu, were screened out by network pharmacology and vascular myograph experiments, among which the effects of salvianolic acid A were dominant. Meanwhile, salvianolic acid A could dilate mesenteric artery in a pressure-dependent manner. Interestingly, salvianolic acid A could still relax the vascular rings under the stimulation of KCl and Bayk8644, two agonists of L-type calcium channel. By contrast, inhibitors of Kir, Kv, Katp and BKCa channels did not block the effect of salvianolic acid A on vasodilation. Salvianolic acid A alleviated Ca2+ transient, referring to changes of intracellular calcium, induced by PE, Bayk8644 and high K+ in the VSMCs. Salvianolic acid A could partially restore the vasodilation function of vascular smooth muscle damaged by AngII and ET-1 induced hypertension situation. CONCLUSIONS: Our results indicate that salvianolic acid A is the major vasodilator substance in DHI and the vasorelaxation pharmacology mechanism involved in inhibiting the L-type calcium channel signaling in smooth muscle cell. Hence, there are potential therapeutic effects of taking salvianolic acid A preparation which may be beneficial to protect cardiovascular system and reduce blood pressure.

[Network Meta-analysis of efficacy and safety of Chinese patent medicines in treatment of ankylosing spondylitis].

To evaluate the efficacy and safety of Chinese patent medicines in the treatment of ankylosing spondylitis(AS) by frequency network Meta-analysis. Randomized controlled trials(RCTs)of Chinese patent medicines for AS were retrieved from CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library databases from the time of database establishment to January 2021. The quality of the included RCTs was evaluated according to the Cochrane bias risk standard, and the data was analyzed by RevMan 5.3 and Stata/MP 15.1. A total of 12 kinds of Chinese patent medicines in 55 RCTs were included. According to Meta-analysis, in term of the effectiveness, the top three optimal medication regimens were Biqi Capsules, Yishen Juanbi Pills and Yaobitong Capsules combined with western medicine. The top three interventions to reduce the erythrocyte sedimentation rate(ESR)were Yishen Juanbi Pills, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. The top three interventions to reduce the C-reactive protein(CRP)were Biqi Capsules, Xianling Gubao Capsules and Fufang Xuanju Capsules combined with western medicine. In terms of the safety, top three optimal medication regimens were Total Glucosides of Paeony Capsules, Yishen Juanbi Pills, and Wangbi Tablets combined with western medicine. This network Meta-analysis suggests that Chinese patent medicines combined with conventional western medicine can effectively improve the joint pain symptoms of AS patients and reduce the acute inflammatory indicators, with high safety. However, the literature included in this study is generally of low methodological quality, and the conclusion needs to be verified by high-quality research.

The Impact of Traditional Chinese Medicine QingreHuoxue Treatment and the Combination of Methotrexate and Hydroxychloroquine on the Radiological Progression of Active Rheumatoid Arthritis: A 52-Week Follow-Up of a Randomized Controlled Clinical Study.

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). QingreHuoxue treatment (QingreHuoxue decoction [QRHXD]/QingreHuoxue external preparation [QRHXEP]) is a Chinese medicine treatment for RA. To date, very few studies have compared the long-term effects of QRHXD with those of conventional disease-modifying antirheumatic drugs on RA disease activity and radiological progression. QRHXD delayed the radiological progression and showed long-term clinical efficacy of RA. In clinical experiments, the clinical evidence of delaying the radiological progression of RA patients was obtained. A portion of the patients who participated in the "Traditional Chinese Medicine QingreHuoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis" study were followed up for 52 weeks, and intention-to-treat (ITT) and compliance protocol (PP) analyses were used to collect and compare the clinical indicators and imaging data between baseline and week 52. Two radiologists who were blind to treatment scored the images independently. Of the 468 subjects, 141 completed the 52-week follow-up. There were no significant differences among the three groups: the traditional Chinese medicine comprehensive treatment group, the Western medicine treatment group, and the integrated traditional Chinese and Western medicine treatment group. There were no differences in the total Sharp score, joint space stenosis score, and joint erosion score at baseline or 52 weeks. In the comparison of the estimated annual radiographic progression (EARP) and the actual annual Sharp total score changes among the three groups, the actual changes were much lower than the EARP at baseline. The radiological progress in all three groups was well controlled. Results of the ITT and PP data sets showed that the disease activity score 28 level of the three groups at 52 weeks was significantly lower than that at baseline. During the 52-week treatment period, the clearance of heat and promotion of blood circulation controlled disease activity and delayed the radiological progress of active RA.

Photo-Enhanced Chemotherapy Performance in Bladder Cancer Treatment via Albumin Coated AIE Aggregates.

The implementation of cisplatin-based neoadjuvant chemotherapy (NAC) plays a key role in conjunction with surgical resection in preventing bladder cancer progression and recurrence. However, the significant dose-dependent toxic side effects of NAC are still a major challenge. To solve this problem, we developed a photoenhanced cancer chemotherapy (PECC) strategy based on AIEgen ((E)-3-(2-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1,1-dimethyl-1H-3λ4-benzo[e]indol-3-yl)propane-1-sulfonate), which is abbreviated as BITT. Multifunctional BITT@BSA-DSP nanoparticles (NPs) were employed with an albumin-based nanocarrier decorated with the cisplatin(IV) prodrug and loaded to produce strong near-infrared fluorescence imaging (NIR FLI), and they exhibited good photoenhancement performance via photodynamic therapy (PDT) and photothermal therapy (PTT). In vitro results demonstrated that BITT@BSA-DSP NPs could be efficiently taken up by bladder cancer cells and reduced to release Pt (II) under reductase, ensuring the chemotherapy effect. Furthermore, both in vitro and in vivo evaluation verified that the integration of NIR FL imaging-guided PECC efficiently promoted the sensitivity of bladder cancer to cisplatin chemotherapy with negligible side effects. This work provides a promising strategy to enhance the sensitivity of multiple cancers to chemotherapy drugs and even achieve effective treatments for drug-resistant cancers.

Immediate acupuncture with GB34 for biliary colic: protocol for a randomised controlled neuroimaging trial.

INTRODUCTION: As the main manifestation of gallstone disease, biliary colic (BC) is an episodic attack that brings patients severe pain in the right upper abdominal quadrant. Although acupuncture has been documented with significance to lead to pain relief, the immediate analgesia of acupuncture for BC still needs to be verified, and the underlying mechanism has yet to be covered. Therefore, this trial aims first to verify the immediate pain-alleviation characteristic of acupuncture for BC, then to explore its influence on the peripheral sensitised acupoint and central brain activity. METHODS AND ANALYSIS: This is a randomised controlled, paralleled clinical trial, with patients and outcome assessors blinded. Seventy-two patients with gallbladder stone disease presenting with BC will be randomised into a verum acupuncture group and the sham acupuncture group. Both groups will receive one session of immediate acupuncture treatment. Improvements in patients' BC will be evaluated by the Numeric Rating Scale, and the pain threshold of acupoints will also be detected before and after treatment. During treatment, brain neural activity will be monitored with functional near-infrared spectroscopy (fNIRS), and the needle sensation will be rated. Clinical and fNIRS data will be analysed, respectively, to validate the acupuncture effect, and correlation analysis will be conducted to investigate the relationship between pain relief and peripheral-cerebral functional changes. ETHICS AND DISSEMINATION: This trial has been approved by the institutional review boards and ethics committees of the First Teaching Hospital of Chengdu University of Traditional Chinese Medicine, with the ethical approval identifier 2019 KL-029, and the institutional review boards and ethics committees of the First People's Hospital of Longquanyi District, with the ethical approval identifier AF-KY-2020071. The results of this trial will be disseminated through peer-reviewed publications and conference abstracts or posters. TRIAL REGISTRATION NUMBER: CTR2000034432.

Strong Penetration-Induced Effective Photothermal Therapy by Exosome-Mediated Black Phosphorus Quantum Dots.

Nanocancer medicine, such as photothermal therapy (PTT), as a promising way to solve cancer without side effects, faces a huge biological barrier during the circulation of nanoparticles in the body, including nanobiological interactions in the blood, isolation of nanoparticles in the macrophage system, tumor spillover effect, and especially uneven intratumoral distribution of nanoparticles, which cast a shadow over the hope. To address the problem of intratumoral distribution, an effective photothermal agent is introduced by packaging the black phosphorus quantum dots (BPQDs) into exosome vector (EXO) through electroporation method. With the improving and proper stability for better therapy, the resulting BPQDs@EXO nanospheres (BEs) exhibit good biocompatibility, long circulation time, and excellent tumor targeting ability, hence impressive PTT efficiency evidenced by highly efficient tumor ablation in vivo. Importantly, great permeability on organoids contributed by EXO appears with BEs, which strongly promotes the efficient killing ability. These BP-based nanospheres must promise high clinical potential due to the high PTT efficiency and minimal side effects.

Leaf economic strategies of a sclerophyllous plant (Eurya japonica): commonalities and particularities of trait correlation structures in low-moisture and low-phosphorus habitats.

Sclerophylly proves an advantageous strategy in a variety of stressful environments. However, it is less clear how multiple phenotypic traits in sclerophyllous plants are integrated to accomplish proper functions under specific stressors. This study measured 10 leaf traits in a sclerophyllous species, Eurya japonica Thunb., in the Zhoushan Archipelago, eastern China, to examine how the structures of trait correlation (i.e. phenotypic integration) vary between two habitats with contrasting moisture and phosphorus (P) availability. Overall, the trait correlation matrices were similar between the two habitats under study (Mantel r > 0.5), reflecting a consistent trade-off between leaf outspreading (i.e. leaf area/mass ratio) and water-use efficiency (measured by δ13C). Stomatal conductance was correlated with leaf area, thickness and area/mass ratio only in the dry, P-rich habitat, whereas it was robustly correlated with leaf P per unit area in the wet, P-poor habitat. Moreover, leaf water-use efficiency was robustly correlated with leaf P and N per unit area in the dry habitat, but not so in the low-P one. These differences in trait correlation structures illustrate that the pathways of strategic compromise under contrasting stressors were locally specialised. This study highlights the importance of phenotypic integration as an emergent 'trait' in sustaining viable strategies.

Traditional Chinese Medicine Qingre Huoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis: A Multicenter, Double-Blind, Randomized Controlled Trial.

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). Qingre Huoxue treatment (Qingre Huoxue decoction (QRHXD)/Qingre Huoxue external preparation (QRHXEP)) is a therapeutic scheme of TCM for RA. To date, there have been few studies comparing the efficacy and safety of QRHXD and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of active RA. This was investigated in a multicenter, double-blind, randomized controlled trial involving 468 Chinese patients with active RA [disease activity score (DAS)-28 > 3.2] treated with QRHXD/QRHXEP (TCM group), methotrexate plus hydroxychloroquine [Western medicine (WM) group], or both [integrative medicine (IM) group]. Patients were followed up for 24 weeks. The primary outcome measure was the change in DAS-28 from baseline to 24 weeks. The secondary outcome measures were treatment response rate according to American College of Rheumatology 20, 50, and 70% improvement criteria (ACR-20/50/70) and the rate of treatment-related adverse events (TRAEs). The trial was registered at ClinicalTrials.gov (NCT02551575). DAS-28 decreased in all three groups after treatment (p < 0.0001); the score was lowest in the TCM group (p < 0.05), while no difference was observed between the WM and IM groups (p > 0.05). At week 24, ACR-20 response was 73.04% with TCM, 80.17% with WM, and 73.95% with IM (based on the full analysis set [FAS], p > 0.05); ACR-50 responses were 40.87, 47.93, and 51.26%, respectively, (FAS, p > 0.05); and ACR-70 responses were 20.87, 22.31, and 25.21%, respectively, (FAS, p > 0.05). Thus, treatment efficacy was similar across groups based on ACR criteria. On the other hand, the rate of TRAEs was significantly lower in the TCM group compared to the other groups (p < 0.05). Thus, QRHXD/QRHXEP was effective in alleviating the symptoms of active RA-albeit to a lesser degree than csDMARDs-with fewer side effects. Importantly, combination with QRHXD enhanced the efficacy of csDMARDs. These results provide evidence that QRHXD can be used as an adjunct to csDMARDs for the management of RA, especially in patients who experience TRAEs with standard drugs. Clinical Trial Registration: ClinicalTrials.gov, identifier NCTNCT025515.

Effects of bioactive components of Pu-erh tea on gut microbiomes and health: A review.

Pu-erh tea is a post-fermentation tea with unique flavor and multiple health benefits. Due to the various microorganisms involved in the post-fermentation process, Pu-erh tea contains highly complex components, which have rich interactions with the gut microbiomes (GMs). Because the structure and homeostasis of GMs are closely related to human wellness and the various diseases progress, the beneficial effects of Pu-erh tea on GMs have a great potential for application in health care. However, there is no systematic summary of the bioactive components of Pu-erh tea, and their effects on the GMs. Here, we review the current studies on the effects of Pu-erh tea and its bioactive components on the structure of GMs as well as on health improvement, and further discuss the relevant quality indicators. This "components - function - indicators" clue will hopefully stimulate the standardization of Pu-erh tea fermentation process and the development of its functional products.