Climate change-related biodiversity fluctuations and composition changes in an old-growth subtropical forest: A 26-yr study.

The detection and attribution of biodiversity change is of great scientific interest and central to policy effects aimed at meeting biodiversity targets. Yet, how such a diverse climate scenarios influence forest biodiversity and composition dynamics remains unclear, particularly in high diversity systems of subtropical forests. Here we used data collected from the permanent sample plot spanning 26 years in an old-growth subtropical forest. Combining various climatic events (extreme drought, subsequent drought, warming, and windstorm), we analyzed long-term dynamics in multiple metrics: richness, turnover, density, abundance, reordering and stability. We did not observe consistent and directional trends in species richness under various climatic scenarios. Still, drought and windstorm events either reduced species gains or increased species loss, ultimately increased species turnover. Tree density increased significantly over time as a result of rapid increase in smaller individuals due to mortality in larger trees. Climate events caused rapid changes in dominant populations due to a handful of species undergoing strong increases or declines in abundance over time simultaneously. Species abundance composition underwent significant changes, particularly in the presence of drought and windstorm events. High variance ratio and species synchrony weaken community stability under various climate stress. Our study demonstrates that all processes underlying forest community composition changes often occur simultaneously and are equally affected by climate events, necessitating a holistic approach to quantifying community changes. By recognizing the interconnected nature of these processes, future research should accelerate comprehensive understanding and predicting of how forest vegetation responds to global climate change.

Electroacupuncture Alleviates Lung Injury in CpG1826-Challenged Mice via Modulating CD39-NLRP3 Pathway.

Purpose: Cytokine storm secondary lung injury (CSSLI) is the leading death cause in COVID-19 virus infection, and CD39-dominated purinergic brake drives NLRP3 inflammasome activation and pyroptosis, which plays a crucial role in the pathogenesis of CSSLI. Though electroacupuncture (EA) can alleviate lung injury caused by a variety of inducers, its effect on CSSLI and the underlying mechanism needs further investigation. Methods: We established a widely recognized CSSLI mice model with CpG1826 (CpG), a TLR-9 agonist agent. Luminex liquid chip was employed to detect serum levels of 12 cytokines/chemokines to evaluate cytokine storm formation. H+E staining and transmission electron microscope were applied to examine pulmonary pathological injury and alveolar macrophage structure, respectively. IL-1ß, IL-18, IL-1α, and HMGB-1 in BAL fluid were determined by ELISA kits. mRNA and protein levels of lung CD39 and NLRP3 were assessed by qRT-PCR and Western blotting. An in vitro model was also established by incubating PMA-differentiated THP-1 cells with serum samples obtained from relevant group of mice. Results: Repeated CpG induced CSSLI together with the elevation of 11 cytokines/chemokines including GM-CSF, IL-16, IL-1α, MCP-1, IL-2, IL-10, CCL3, IL-1ß, TNF-α, IL-6, and IL-17A, though not IFN-γ, which was reduced by EA pretreatment to a different extent. EA also alleviated lung injury and recovered lung macrophage structure. Moreover, CpG enhanced IL-1ß and IL-18 level in BAL fluid, promoted NLRP3, while suppressing CD39 expression in lung, all of which were reversed by EA pretreatment. Of note, EA failed to further decrease BAL fluid IL-1ß, IL-18, IL-1α, and HMGB-1 levels when A438079, a selective inhibitor of P2X7, was administered. However, both CD39 and NLRP3 are dispensable for EA decreasing multi-cytokine secretion in serum-incubated and CpG-stimulated THP-1 cells. Taken together, EA alleviated CSSLI in CpG-challenged mice by regulating the CD39-NLRP3 pathway in a P2X7-dependent way. Conclusion: EA demonstrated potential to be applied in COVID-19 treatment.

Suitability of R. pulmo Jellyfish-Collagen-Coated Well Plates for Cytocompatibility Analyses of Biomaterials.

Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/-12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.

Research on Service Design for People with Mental Disorders: Take Curing Digital Cloud Tourism App Media in the Post-Epidemic Era as an Example.

In today's era, the number of people suffering from mental disorders has increased significantly, which has become a public health event, and its treatment plans and means are difficult, especially in the special environment of the post-epidemic era, traditional simple treatment cannot meet the ever-changing diseases. This article from the current situation of mental health and its treatment environment in our country, in the face of mental disorder crowd healing the practical significance of the innovation design, digital media curative cloud travel APP the research path of service design, technical implementation, operation methods, innovative thinking dimensions to explore how to age for people in the face of disorder in the outbreak of curative services digital media design. In order to provide some reference and reference value for the development of spiritual healing industry, the design ideas and methods of smart cloud tourism APP service are designed and studied in terms of user travel experience, service process optimization, service interface innovation and service contact point design.

Alkaloids from Aconitum carmichaelii Alleviates DSS-Induced Ulcerative Colitis in Mice via MAPK/NF-κB/STAT3 Signaling Inhibition.

Fuzi (Aconitum carmichaelii Debx) has been traditionally used for the treatment of ulcerative colitis (UC) in China for thousands of years. The total alkaloids of A. carmichaelii (AAC) have been considered as the main medicinal components of fuzi, whereas its underlying anti-UC mechanisms remain elusive. In the present study, the dextran sulfate sodium (DSS)-induced UC mice model, which was consistent with the symptoms and pathological features of human UC, was established to comprehensively evaluate the anti-UC effects of AAC. The results indicated that AAC effectively improved the weight loss, disease activity index (DAI), spleen hyperplasia, and colon shortening, and thus alleviated the symptoms of UC mice. Meanwhile, AAC not only inhibited the MPO enzyme and the abnormal secretion of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IFN-γ, and IL-17A) and suppressed the overexpression of inflammatory mediators (TNF-α, IL-1ß, and IL-6) of mRNA but also reduced the phosphorylation of p38 MAPK, ERK, and JNK, and the protein expressions of NF-κB, IκB-α, STAT3, and JAK2 in the colon tissue. Furthermore, the LC-MS/MS quantitative determination suggested that the three low toxic monoester alkaloids were higher in both contents and proportion than that of the three high toxic diester alkaloids. Additionally, molecular docking was hired to investigate the interactions between alkaloid-receptor complexes, and it suggested the three monoester alkaloids exhibited higher binding affinities with the key target proteins of MAPK, NF-κB, and STAT3. Our finding showcased the noteworthy anti-UC effects of AAC based on the MAPK/NF-κB/STAT3 signaling pathway, which would provide practical and edge-cutting background information for the development and utilization of A. carmichaelii as a potential natural anti-UC remedy.

A Traditional Chinese Medicine Formula Danshen Baibixiao Ameliorates Imiquimod-Induced Psoriasis-Like Inflammation in Mice.

Background: Danshen Baibixiao (DB) is a traditional Chinese medicine formula, which has been used to treat psoriasis for decades. Although DB shows good efficacy in clinical practice, the pharmacological effects and underlying mechanisms of DB remain elusive. This study aimed to evaluate the anti-psoriatic effects of DB and explore its underlying mechanisms in an imiquimod (IMQ)-induced psoriasis-like mouse model. Materials and methods: DB was orally administered on IMQ-induced psoriatic mice. Psoriasis area severity index (PASI) was used to evaluate the severity of the inflammation in skin, and histological changes were evaluated by hematoxylin and eosin (H and E) staining. Levels of inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-17A, IL-23, IL-6, IL-1ß and IL-22 in serum were assessed by enzyme-linked immunosorbent assay (ELISA). mRNA expressions of IL-17A, IL-23, IL-6 and IL-22 were determined by real-time polymerase chain reaction (PCR). Expression levels of proteins related to NF-κB, STAT3 and MAPKs signaling pathways were measured by western blotting (WB). Results: DB significantly ameliorated the psoriatic symptoms in IMQ-induced mice. The serum levels of inflammatory cytokines (TNF-α, IL-17A, IL-23, IL-6, IL-1ß and IL-22) were decreased, and mRNA expressions of IL-17A, IL-23, IL-6 and IL-22 in skin tissues were down-regulated. Moreover, WB analysis indicated that DB inhibited the activation of NF-κB, STAT3 and MAPKs signaling pathways. Conclusion: This study confirms the anti-psoriatic activity of DB in IMQ-induced psoriasis-like mice. The possible mechanism may relate to the activities of regulating the IL-23/TH-17 axis and suppressing the activation of NF-κB, STAT3 and MAPKs signaling pathways.

Enhanced Bioavailability of Dihydrotanshinone I-Bovine Serum Albumin Nanoparticles for Stroke Therapy.

Dihydrotanshinone I (DHT) is a natural component in Salvia miltiorrhiza and has been widely researched for its multiple bioactivities. However, poor solubility and biocompatibility of DHT limit its desirable application for clinical purposes. Herein, DHT was encapsulated with bovine serum albumin (BSA) to enhance bioavailability. Compared to free DHT, DHT-BSA NPs (nanoparticles) showed an improved solubility in normal saline and increased protection against hydrogen peroxide-induced oxidative damage in PC12 cells. In addition, DHT-BSA NPs administered by intravenous injection displayed a significant efficacy in the middle cerebral artery occlusion/reperfusion models, without any impact on the cerebral blood flow. In summary, DHT-BSA NPs show an enhanced bioavailability compared with free DHT and a successful penetration into the central nervous system for stroke therapy, demonstrating their application potential in cardio-cerebrovascular diseases.

Characterization of the complete chloroplast genome of Melaleuca cajuputi subsp. cumingiana (Myrtaceae).

Plants in the genus Melaleuca have been widely used as traditional medicine mainly because of their broad spectrum antimicrobial activity. In this study, we reported the complete chloroplast genome of Melaleuca cajuputi subsp. cumingiana. The chloroplast genome of this species is 158,855 bp in length, including a pair of inverted repeat regions (IRs) (26,727 bp) that is divided by a large single-copy (LSC) area (87,338 bp) and a small single-copy (SSC) area (18,063 bp). The circular chloroplast genome of M. cajuputi subsp. cumingiana contains 135 unique genes, composing of 87 protein-coding genes, 40 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicates that M. cajuputi subsp. cumingiana was clustered with species in the tribe Melaleuceae. This complete chloroplast genome of M. cajuputi subsp. cumingiana will provide a powerful tool to accelerate breeding, biotechnological and phylogenetic study.

Qingxue jiedu formulation ameliorated DNFB-induced atopic dermatitis by inhibiting STAT3/MAPK/NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingxue jiedu Formulation (QF) is composed of two classic prescriptions which have been clinically used for more than 5 centuries and appropriately modified through basic theory of traditional Chinese medicine for treating various skin inflammation such as atopic dermatitis (AD), acute dermatitis and rash. Although QF possesses a prominent clinical therapeutic effect, seldom pharmacological studies on its anti-AD activity are conducted. AIM OF THE STUDY: We used AD mice model to investigate the anti-AD activities of QF, as well as its underlying molecular mechanisms which involved signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. MATERIALS AND METHODS: 2,4-dinitrofluorobenzene (DNFB)-induced AD mice were used to collect serum and skin tissues for consequential determination. The levels of various inflammatory factors [interleukin (IL)-12, Interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-4, IL-6 and immunoglobulin E (IgE)] were determined by enzyme-linked immunosorbent assay (ELISA). Real-time polymerase chain reaction (RT-PCR) was contributed to detect the effects of relevant inflammatory factors on mRNA. The roles of STAT3, NF-κB and MAPK signaling pathways in AD response were analyzed by Western blotting (WB), and the thickening of mice dorsal skin and inflammatory cell infiltration were observed by hematoxylin and eosin (H&E) staining. RESULTS: QF significantly reduced the skin thickening, inflammatory cell infiltration and other symptoms in AD mice. The levels of IL-12, TNF-α, IL-4, IL-6 and IgE were decreased, while IFN-γ was increased by QF in the ELISA analysis. QF lessened the levels of lL-6 and elevated IFN-γ on the mRNA level. In addition, WB analysis showed QF thoroughly inhibited the activation of NF-κB, STAT3 and phosphorylation of JAK1, JAK2, JAK3, while partially suppressed MAPK signaling pathways. CONCLUSIONS: QF inhibited the activations of STAT3, MAPK and NF-κB signaling pathways and possessed a significant therapeutic effect on AD. Therefore, QF deserves our continuous attention and research as a prominent medicine for AD.

Intestinal anti-inflammatory effects of fuzi-ganjiang herb pair against DSS-induced ulcerative colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi and ganjiang are widely used as traditional Chinese medicines (TCM) in China, Korea, Japan, and many other southeast Asian countries for treating ulcerative colitis (UC), emesis and heart failure for more than 1800 years. However, the underlying mechanism of fuzi, ganjiang and fuzi-ganjiang herb pair is still unclear. In our study, we explored the therapeutic effects of fuzi, ganjiang and fuzi-ganjiang herb pair against dextran sulfate sodium (DSS)-induced UC in mice model, along with the relevant mechanism. MATERIALS AND METHODS: The contents of each marker compound in fuzi decoction (FD), ganjiang decoction (GD) and fuzi-ganjiang decoction (FGD) were determined using LC-MS/MS. During the experiment, bodyweight changes in each group were monitored every 5 days. On the day of sacrifice, colonic length, disease activity index (DAI) and spleen weight were also evaluated and histopathological examination was performed through hematoxylin & eosin (H&E) staining. The levels of myeloperoxidase (MPO) and inflammatory cytokines in colon tissues were determined by enzyme-linked immunosorbent assay (ELISA), and then the relative mRNA productions of inflammatory mediators, such as MPO, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were measured by real-time polymerase chain reaction (PCR). Involvement of MAPK, STAT3 and NF-κB signaling pathways in the pathogenesis of UC was determined in each group using Western Blot (WB) analysis. RESULTS: Compared with fuzi and ganjiang single decoction, the content of the alkaloids derived from fuzi (especially the diester alkaloid with strong toxicity, hypaconitine) in fuzi-ganjiang herb pair decoction was reduced. Additionally, the 6-gingerol, which was not found in ganjiang single decoction, was retained in fuzi-ganjiang herb pair decoction. FD, GD, and FGD significantly restored the bodyweight reduction, colon shortening, DAI elevation, splenomegaly and histological score in DSS-induced UC mice. Furthermore, except for the failure of low dosage of ganjiang decoction (GD-L) on IL-17A, all FD, GD and FGD significantly inhibited the production of MPO and inflammatory cytokines, such as IFN-γ, TNF-α, IL-1ß, IL-6, IL-10 and IL-17A, and suppressed the relative expression of inflammatory mediators, such as MPO, iNOS and COX-2 mRNA in colon tissues of DSS-induced mice. According to WB analysis, fuzi, ganjiang and fuzi-ganjiang combination inhibited the activation of MAPK, NF-κB and STAT3 signaling pathways. CONCLUSIONS: Our study demonstrated that fuzi, ganjiang and fuzi-ganjiang combination possess prominent anti-inflammatory activities against DSS-induced UC mice; the involved mechanism may be related to inhibition the activation of MAPK, NF-κB, and STAT3 signaling pathways.

The dietary freeze-dried fruit powder of Actinidia arguta ameliorates dextran sulphate sodium-induced ulcerative colitis in mice by inhibiting the activation of MAPKs.

In this study, we aimed at investigating the antiinflammatory activity of the freeze-dried fruit powder of Actinidia arguta (FAA) on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice and the effect of its extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. For pharmacodynamic studies, the oral administration of FAA (300 or 600 mg kg-1) could decrease the disease activity index (DAI), reduce the incidence of colon and spleen edemas (caused by inflammation), and alleviate the pathological changes in UC. For research involving biochemical indicators, FAA could decrease the expression of inflammatory markers (such as myeloperoxidase (MPO)) and attenuate the oxidative stress levels. ELISA results revealed that the expressions of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) were downregulated by FAA. Furthermore, the expression levels of the inflammation-induced activation of p38, JNK, and ERK were decreased by FAA. Hence, it was concluded that FAA could alleviate the UC symptoms in mice and the inflammatory response of macrophages via the MAPK signal pathway. Overall, FAA might have the potential to treat UC when used as a dietary supplement.

[Effects of curcumin on tumor growth and immune function in prostate cancer-bearing mice].

OBJECTIVE: To explore the effects of curcumin (CCM) on tumor growth and immune function in mice bearing RM-1 prostate cancer cells. METHODS: A prostate cancer model was established in 50 C57BL/6 mice by subcutaneous inoculation of RM-1 cells. The model mice were randomly assigned to intraperitoneal injection of 10% dimethyl sulfoxide at 0.2 ml (the model control group), cyclophosphamide at 20 mg/kg (the CTX group), or CCM at 50 mg/kg (the low-dose CCM group), 100 mg/kg (the medium-dose CCM group) or 200 mg/kg (the high-dose CCM group), respectively, all once a day for 14 successive days, followed by measurement of the tumor weight, calculation of the tumor-inhibition rate, and detection of immunological indicators. RESULTS: The tumor weight was significantly decreased in the CTX (ï¼»1.32 ± 0.06ï¼½ g), low-dose CCM (ï¼»1.1.54 ± 0.08ï¼½ g), medium-dose CCM (ï¼»1.48 ± 0.08ï¼½ g), and high-dose CCM groups (ï¼»1.42 ± 0.07ï¼½ g) as compared with that in the model control group (ï¼»2.09 ± 0.10ï¼½ g) (P < 0.05 or P < 0.01), with no statistically significant differences among the former four groups (P > 0.05). The tumor-inhibition rates in the CTX and low-, medium- and high-dose CCM groups were 36.84%, 27.27%, 29.18% and 32.06%, respectively. All the immunological indicators except the CD4+/CD8+ ratio were remarkably reduced in the CTX group as compared with those in the model control (P < 0.01), but increased in the CCM groups in comparison with those in the CTX group (P < 0.01). CONCLUSIONS: Curcumin has an anti-tumor effect and enhances immune function in prostate cancer-bearing mice.

[Design and experiment of a multi-modal electroencephalogram-near infrared spectroscopy helmet for simultaneously acquiring at the same brain area].

Multi-modal brain-computer interface and multi-modal brain function imaging are developing trends for the present and future. Aiming at multi-modal brain-computer interface based on electroencephalogram-near infrared spectroscopy (EEG-NIRS) and in order to simultaneously acquire the brain activity of motor area, an acquisition helmet by NIRS combined with EEG was designed and verified by the experiment. According to the 10-20 system or 10-20 extended system, the diameter and spacing of NIRS probe and EEG electrode, NIRS probes were aligned with C3 and C4 as the reference electrodes, and NIRS probes were placed in the middle position between EEG electrodes to simultaneously measure variations of NIRS and the corresponding variation of EEG in the same functional brain area. The clamp holder and near infrared probe were coupled by tightening a screw. To verify the feasibility and effectiveness of the multi-modal EEG-NIRS helmet, NIRS and EEG signals were collected from six healthy subjects during six mental tasks involving the right hand clenching force and speed motor imagery. These signals may reflect brain activity related to hand clenching force and speed motor imagery in a certain extent. The experiment showed that the EEG-NIRS helmet designed in the paper was feasible and effective. It not only could provide support for the multi-modal motor imagery brain-computer interface based on EEG-NIRS, but also was expected to provide support for multi-modal brain functional imaging based on EEG-NIRS.

[Control of intelligent car based on electroencephalogram and neurofeedback].

To improve the performance of brain-controlled intelligent car based on motor imagery (MI), a method based on neurofeedback (NF) with electroencephalogram (EEG) for controlling intelligent car is proposed. A mental strategy of MI in which the energy column diagram of EEG features related to the mental activity is presented to subjects with visual feedback in real time to train them to quickly master the skills of MI and regulate their EEG activity, and combination of multi-features fusion of MI and multi-classifiers decision were used to control the intelligent car online. The average, maximum and minimum accuracy of identifying instructions achieved by the trained group (trained by the designed feedback system before the experiment) were 85.71%, 90.47% and 76.19%, respectively and the corresponding accuracy achieved by the control group (untrained) were 73.32%, 80.95% and 66.67%, respectively. For the trained group, the average, longest and shortest time consuming were 92 s, 101 s, and 85 s, respectively, while for the control group the corresponding time were 115.7 s, 120 s, and 110 s, respectively. According to the results described above, it is expected that this study may provide a new idea for the follow-up development of brain-controlled intelligent robot by the neurofeedback with EEG related to MI.

Anti-Inflammatory Effects of p-Coumaric Acid, a Natural Compound of Oldenlandia diffusa, on Arthritis Model Rats.

OBJECTIVES: In China, Oldenlandia diffusa (OD) is a natural herb that is widely used and has been proven to be effective in the treatment of rheumatoid arthritis (RA). This study aimed to preliminarily reveal the mechanism by which OD exerts its beneficial effect. METHODS: Ultra-performance liquid chromatography photodiode array was applied to identify the absorbable compounds in the plasma of collagen-induced arthritis (CIA) model rats. After 2 weeks, an OD decoction or the identified absorbable compound was administered to CIA rats. Morphology, X-ray images of the joints, pathological images, arthritis index, and cytokine (TNF-α and IL-6) levels were evaluated. RESULTS: p-Coumaric acid (p-CA) was identified as the absorbed compound in plasma. After administration of p-CA solution or the OD decoction, symptoms in the treated rats were alleviated as compared to the untreated model rats, and inflammatory cell infiltration was suppressed. The arthritis index and serum levels of TNF-α and IL-6 were decreased as compared to the control group. CONCLUSIONS: OD may exert its anti-inflammatory effect on RA via its active ingredient, p-CA. This information sheds light on the mechanism by which OD exerts its anti-inflammatory effort in RA and forms the basis for further development of therapeutic agents for RA.

Evidence-based review of oral traditional Chinese medicine compound recipe administration for treating weight drop-induced experimental traumatic brain injury.

BACKGROUND: Recently, a number of studies conducted and published in China have suggested that traditional Chinese medicine compound recipe (TCMCR) may be beneficial in the treatment of experimental traumatic brain injury (TBI). In this study, we conducted a systematic review and meta-analysis of the efficacy of TCMCR in TBI model with weight drop method to provide robust evidence on the effects of TCMCR and to determine whether TCMCR can be recommended for routine treatment or considered as a standard treatment for TBI. METHODS: We identified eligible studies by searching five electronic databases on April 1, 2014, and pooled the data using the random-effects model. Results were reported in terms of standardized mean difference (SMD). We also calculated statistical heterogeneity, evaluated the studies' methodological quality and investigated the presence of publication bias. RESULTS: Totally, 187 relevant publications were searched from databases, 25 of which met our inclusion criteria. The overall methodological quality of the most studies was poor, and there was evidence of statistical heterogeneity among studies along with small-study effects. Meta-analysis showed statistically significant effects indicating that TCMCR has a beneficial effect on TBI. CONCLUSIONS: Despite the limitations, we concluded that TCMCR may reduce brain water content, improve BBB permeability, and decrease TNF-α/NO expression after experimental TBI in terms of overall efficacy. However, our review also indicates that more well-designed and well-reported animal studies are needed.

Study design and implementation for population pharmacokinetics of Chinese medicine: An expert consensus.

Although many population pharmacokinetics (PPK) researches have been conducted on chemical drugs, few have been in the field of Chinese medicine (CM). Each ingredient in CMs possesses different pharmacokinetic characteristics, therefore, it is important to develop methods of PPK studies on them to identify the differences in CM drug safety and efficacy among the population subgroups and to conduct quantitative studies on the determinants of CM drug concentrations. To develop an expert consensus on study design and implementation for PPK of CM, in August 2013, 6 experts in the field of PPK, CMs pharmacology, and statistics discussed problems on the PPK research protocol of CMs, and a consensus was reached. The medicines with toxicity and narrow therapeutic windows and with wide range of target population or with frequent adverse reactions were selected. The compositions with definite therapeutic effects were selected as indices, and specific time points and sample sizes were designed according to standard PPK design methods. Target components were tested through various chromatography methods. Total quantity statistical moment analysis was used to estimate PPK parameters of each component and PPK models reflecting the trend of CMs (which assists in reasonable adjustments on clinical dosage). This consensus specifies the study design and implementation process of PPK. It provides guidance for the following: post-marketing clinical studies, in vivo investigations related to the metabolism in different populations, and development and clinical adjustment of dosages of CMs.

The earliest unequivocally modern humans in southern China.

The hominin record from southern Asia for the early Late Pleistocene epoch is scarce. Well-dated and well-preserved fossils older than ∼45,000 years that can be unequivocally attributed to Homo sapiens are lacking. Here we present evidence from the newly excavated Fuyan Cave in Daoxian (southern China). This site has provided 47 human teeth dated to more than 80,000 years old, and with an inferred maximum age of 120,000 years. The morphological and metric assessment of this sample supports its unequivocal assignment to H. sapiens. The Daoxian sample is more derived than any other anatomically modern humans, resembling middle-to-late Late Pleistocene specimens and even contemporary humans. Our study shows that fully modern morphologies were present in southern China 30,000-70,000 years earlier than in the Levant and Europe. Our data fill a chronological and geographical gap that is relevant for understanding when H. sapiens first appeared in southern Asia. The Daoxian teeth also support the hypothesis that during the same period, southern China was inhabited by more derived populations than central and northern China. This evidence is important for the study of dispersal routes of modern humans. Finally, our results are relevant to exploring the reasons for the relatively late entry of H. sapiens into Europe. Some studies have investigated how the competition with H. sapiens may have caused Neanderthals' extinction (see ref. 8 and references therein). Notably, although fully modern humans were already present in southern China at least as early as ∼80,000 years ago, there is no evidence that they entered Europe before ∼45,000 years ago. This could indicate that H. neanderthalensis was indeed an additional ecological barrier for modern humans, who could only enter Europe when the demise of Neanderthals had already started.

Anti-Inflammatory Effects of the Bioactive Compound Ferulic Acid Contained in Oldenlandia diffusa on Collagen-Induced Arthritis in Rats.

Objectives. This study aimed to identify the active compounds in Oldenlandia diffusa (OD) decoction and the compounds absorbed into plasma, and to determine whether the absorbed compounds derived from OD exerted any anti-inflammatory effects in rats with collagen induced arthritis (CIA). Methods. The UPLC-PDA (Ultra Performance Liquid Chromatography Photo-Diode Array) method was applied to identify the active compounds both in the decoction and rat plasma. The absorbable compound was administered to the CIA rats, and the effects were dynamically observed. X-ray films of the joints and HE stain of synovial tissues were analyzed. The levels of IL-1 ß and TNF- α in the rats from each group were measured by means of ELISA. The absorbed compound in the plasma of CIA rats was identified as ferulic acid (FA), following OD decoction administration. Two weeks after the administration of FA solution or OD decoction, the general conditions improved compared to the model group. The anti-inflammatory effect of FA was inferior to that of the OD decoction (P < 0.05), based on a comparison of IL-1 ß TNF- α levels. FA from the OD decoction was absorbed into the body of CIA rats, where it elicited anti-inflammatory responses in rats with CIA. Conclusions. These results suggest that FA is the bioactive compound in OD decoction, and FA exerts its effects through anti-inflammatory pathways.