Global patterns of human-wildlife spatial associations and implications for differentiating conservation strategies.

Understanding the global patterns of human and wildlife spatial associations is essential for pragmatic conservation implementation, yet analytical foundations and indicator-based assessments that would further this understanding are lacking. We integrated the global distributions of 30,664 terrestrial vertebrates and human pressures to map human-nature index (HNI) categories that indicate the extent and intensity of human-wildlife interactions. Along the 2 dimensions of biodiversity and human activity, the HNI allowed placement of terrestrial areas worldwide in one of 4 HNI categories: anthropic (human-dominated areas), wildlife-dominated (little human influence and rich in wildlife), co-occurring (substantial presence of humans and wildlife), and harsh-environment (limited presence of humans and wildlife) areas. The HNI varied considerably among taxonomic groups, and the leading driver of HNI was global climate patterns. Co-occurring regions were the most prevalent (35.9%), and wildlife-dominated and anthropic regions encompassed 26.45% and 6.50% of land area, respectively. Our results highlight the necessity for customizing conservation strategies to regions based on human-wildlife spatial associations and the distribution of existing protected area networks. Human activity and biodiversity should be integrated for complementary strategies to support conservation toward ambitious and pragmatic 30×30 goals.

Patrones globales de las asociaciones espaciales entre humanos y fauna y las implicaciones para la diferenciación de las estrategias de conservación Resumen Es esencial entender los patrones globales de asociaciones entre humanos y fauna para la implementación pragmática de la conservación. Aun así, son muy pocos los fundamentos analíticos y las evaluaciones basadas en indicadores que incrementarían este conocimiento. Integramos la distribución global de 30,664 vertebrados terrestres y presiones humanas para mapear las categorías del índice de naturaleza humana (INH) que indican la extensión e intensidad de las interacciones humano­fauna. El INH permitió la colocación de áreas terrestres en todo el mundo en las dos dimensiones de la biodiversidad y las actividades humanas dentro de una de las cuatro categorías del INH: áreas antrópicas (dominadas por humanos), dominadas por fauna (poca influencia humana y rica en fauna), co­ocurrentes (presencia sustancial de humanos y fauna) y de ambiente severo (presencia limitada de humanos y fauna). El INH varió considerablemente entre los taxones, y el factor principal fueron los patrones climáticos mundiales. Las regiones co­ocurrentes fueron las más frecuentes (35.9%) las regiones antrópicas y dominadas por fauna englobaron el 26.45% y 6.50% del área terrestre respectivamente. Nuestros resultados enfatizan la necesidad de personalizar las estrategias de conservación acorde a la región con base en las asociaciones espaciales entre humanos y fauna y la distribución de las redes existentes de áreas protegidas. La actividad humana y la biodiversidad deberían estar integradas para las estrategias complementarias para respaldar a la conservación hacia los objetivos ambiciosos y pragmáticos de 30 para el 30.

Profile of the gut microbiota of Pacific white shrimp under industrial indoor farming system.

The gut microbial communities interact with the host immunity and physiological functions. In this study, we investigated the bacterial composition in Litopenaeus vannamei shrimp's gut and rearing water under different host (developmental stage: juvenile and adult; health status: healthy and diseased) and environmental factors (temperature 25 °C and 28 °C; and light intensity: low and high). The PCoA analysis showed that all water samples were clustered together in a quarter, whereas the gut samples spread among three quarters. In terms of functional bacteria, gut samples of adult shrimp, healthy adult shrimp, adult shrimp raised at 28 °C, and juvenile shrimp under high light intensity exhibited a higher abundance of Vibrionaceae compared to each other opposite group. Gut samples of juvenile shrimp, infected adult shrimp, juvenile shrimp with low light intensity, and adult shrimp with a water temperature of 25 °C showed a higher abundance of Pseudoaltromonadaceae bacteria compared to each other opposite group. Gut samples of juvenile shrimp, healthy adult shrimp, adult shrimp raised at a water temperature of 28 °C, and juvenile shrimp with high light intensity showed the higher abundance of Firmicutes/Bacteroidota ratio compared to each other opposite group. Our results showed that L. vannamei juveniles are more sensitive to bacterial infections; besides, water temperature of 28 °C and high light intensity groups were both important conditions improving the shrimp gut bacterial composition under industrial indoor farming systems. KEY POINTS: • Bacteria diversity was higher among shrimp intestinal microbiota compared to the rearing water. • Shrimp juveniles are more sensitive to bacterial infection compared to adults. • Water temperature of 28 °C and high light intensity are recommended conditions for white shrimp aquaculture.

The effectiveness of using giant panda as a surrogate for protecting sympatric species.

The use of umbrella species to promote biodiversity conservation is practiced worldwide. The giant panda (Ailuropoda melanoleuca) an iconic species for world wildlife conservation, that inhabits regions with significant biodiversity. Given that the functions at wildlife of different trophic levels and in different body size groups are different within the ecosystem, it is unknown whether those groups of wildlife co-occurring with giant pandas are each likewise protected. To examine the umbrella effect of giant pandas on sympatric species, we used an extensive dataset of wildlife from more than 78% of giant panda habitats. We analysed the changes in distribution for four wildlife categories (large carnivores, large herbivores, medium carnivores and medium herbivores) using a generalized linear mixed model, and the underlying driving factors using binomial logistic regression models. Changes in forests in giant panda habitats were evaluated using Fragstats. The results have shown that the counts of herbivores and medium carnivores increased significantly during the decade. However, those of large carnivores significantly declined. Forest cover and nature reserves showed significant and positive effects on wildlife in 2001 and 2011, while the human population had significant and negative impacts on the herbivores and carnivores. Our results have also suggested that there has been a slight alleviation in forest fragmentation in areas unaffected by earthquakes. We concluded that the umbrella strategy of using the giant panda as an umbrella species achieved partial success by promoting the recovery of herbivores and medium carnivores. Meanwhile, this has indicated that the strategy was not sufficient for large carnivores, and therefore not enough for local ecosystems, given the critical role of large carnivores. We have suggested integrating habitat patches, controlling human disturbance, and preparing for potential human-wildlife conflict management in the Giant Panda National Park to restore large carnivore populations and maintain ecosystem functioning.

Profibrotic COVID-19 subphenotype exhibits enhanced localized ER-dependent HSP47+ expression in cardiac myofibroblasts in situ.

We recently described a subgroup of autopsied COVID-19 subjects (∼40%), termed 'profibrotic phenotype,' who exhibited clusters of myofibroblasts (Mfbs), which were positive for the collagen-specific chaperone heat shock protein 47 (HSP47+) in situ. This report identifies increased, localized (hot spot restricted) expression of αSMA, COLα1, POSTN and FAP supporting the identity of HSP47+ cells as myofibroblasts and characterizing a profibrotic extracellular matrix (ECM) phenotype. Coupled with increased GRP78 in COVID-19 subjects, these data could reflect induction of the unfolded protein response for mitigation of proteostasis (i.e., protein homeostasis) dysfunction in discrete clusters of cells. ECM shifts in selected COVID-19 subjects occur without significant increases in either global trichrome positive staining or myocardial injury based quantitively on standard H&E scoring. Our findings also suggest distinct mechanism(s) for ECM remodeling in the setting of SARS-CoV-2 infection. The ratio of CD163+/CD68+ cells is increased in hot spots of profibrotic hearts compared with either controls or outside of hot spots in COVID-19 subjects. In sum, matrix remodeling of human COVID-19 hearts in situ is characterized by site-restricted profibrotic mediated (e.g., HSP47+ Mfbs, CD163+ Mφs) modifications in ECM (i.e., COLα1, POSTN, FAP), with a strong correlation between COLα1 and HSP47+cells within hot spots. Given the established associations of viral infection (e.g., human immunodeficiency virus; HIV), myocardial fibrosis and sudden cardiac death, early screening tools (e.g., plasma biomarkers, noninvasive cardiac magnetic resonance imaging) for diagnosis, monitoring and treatment of fibrotic ECM remodeling are warranted for COVID-19 high-risk populations.

Microfat exerts an anti-fibrotic effect on human hypertrophic scar via fetuin-A/ETV4 axis.

BACKGROUND: Hypertrophic scar is a fibrotic disease following wound healing and is characterized by excessive extracellular matrix deposition. Autologous microfat grafting proves an effective strategy for the treatment thereof as it could improve the texture of scars and relieve relevant symptoms. This study aims to explore the potential mechanisms underlying the anti-fibrotic effect of microfat on hypertrophic scars. METHODS: In this study, we injected microfat into transplanted hypertrophic scars in mouse models and investigated the subsequent histological changes and differential expression of mRNAs therein. As for in vitro studies, we co-cultured microfat and hypertrophic scar fibroblasts (HSFs) and analyzed molecular profile changes in HSFs co-cultured with microfat by RNA sequencing. Moreover, to identify the key transcription factors (TFs) which might be responsible for the anti-fibrotic function of microfat, we screened the differentially expressed TFs and transfected HSFs with lentivirus to overexpress or knockdown certain differentially expressed TFs. Furthermore, comparative secretome analyses were conducted to investigate the proteins secreted by co-cultured microfat; changes in gene expression of HSFs were examined after the administration of the potential anti-fibrotic protein. Finally, the relationship between the key TF in HSFs and the microfat-secreted anti-fibrotic adipokine was analyzed. RESULTS: The anti-fibrotic effect of microfat was confirmed by in vivo transplanted hypertrophic scar models, as the number of α-SMA-positive myofibroblasts was decreased and the expression of fibrosis-related genes downregulated. Co-cultured microfat suppressed the extracellular matrix production of HSFs in in vitro experiment, and the transcription factor ETV4 was primarily differentially expressed in HSFs when compared with normal skin fibroblasts. Overexpression of ETV4 significantly decreased the expression of fibrosis-related genes in HSFs at both mRNA and protein levels. Fetuin-A secreted by microfat could also downregulate the expression of fibrosis-related genes in HSFs, partially through upregulating ETV4 expression. CONCLUSIONS: Our results demonstrated that transcription factor ETV4 is essential for the anti-fibrotic effect of microfat on hypertrophic scars, and that fetuin-A secreted by microfat could suppress the fibrotic characteristic of HSFs through upregulating ETV4 expression. Microfat wields an alleviative influence over hypertrophic scars via fetuin-A/ETV4 axis.

Gaps in mammal conservation in China: An analysis with a framework based on minimum area requirements.

Climate change, habitat loss, and human disturbance are major threats to biodiversity. Protecting habitats plays a pivotal role in biodiversity conservation, and there is a global imperative to establish an effective system of protected areas (PAs) to implement habitat conservation and halt biodiversity decline. However, the protected patch size of habitat for a species is just as important for biodiversity conservation as the expansion of areas already under protection. In China, conservation management is often carried out based on administrative divisions. Therefore, here, an analytical conservation management framework was developed based on administrative divisions to assess whether the current network of PAs can effectively meet species' conservation needs using the minimum area requirements (MARs) of species as criteria for medium and large-sized mammals in China. This study found that the MAR of medium and large-sized mammals was larger in the northwest and smaller in the southeast, while taking the Hu line as the dividing line. Precipitation seasonality, elevation, annual mean temperature, and annual precipitation are the main environmental factors driving the distribution of a species MAR. Compared with MAR for each species, the maximum protected patch size of habitat is severely undersized in most provinces where those species primarily distribute, and this is particularly true for large carnivores and threatened species. The densely populated provinces of eastern China are particularly affected by this. The present study's framework can identify the provinces needing to expand PAs or implement other effective area-based conservation measures and habitat restoration. This analytical framework is also relevant for biodiversity conservation in different taxa and regions around the globe.

New insight in urological cancer therapy: From epithelial-mesenchymal transition (EMT) to application of nano-biomaterials.

A high number of cancer-related deaths (up to 90) are due to metastasis and simple definition of metastasis is new colony formation of tumor cells in a secondary site. In tumor cells, epithelial-mesenchymal transition (EMT) stimulates metastasis and invasion, and it is a common characteristic of malignant tumors. Prostate cancer, bladder cancer and renal cancer are three main types of urological tumors that their malignant and aggressive behaviors are due to abnormal proliferation and metastasis. EMT has been well-documented as a mechanism for promoting invasion of tumor cells and in the current review, a special attention is directed towards understanding role of EMT in malignancy, metastasis and therapy response of urological cancers. The invasion and metastatic characteristics of urological tumors enhance due to EMT induction and this is essential for ensuring survival and ability in developing new colonies in neighboring and distant tissues and organs. When EMT induction occurs, malignant behavior of tumor cells enhances and their tend in developing therapy resistance especially chemoresistance promotes that is one of the underlying reasons for therapy failure and patient death. The lncRNAs, microRNAs, eIF5A2, Notch-4 and hypoxia are among common modulators of EMT mechanism in urological tumors. Moreover, anti-tumor compounds such as metformin can be utilized in suppressing malignancy of urological tumors. Besides, genes and epigenetic factors modulating EMT mechanism can be therapeutically targeted for interfering malignancy of urological tumors. Nanomaterials are new emerging agents in urological cancer therapy that they can improve potential of current therapeutics by their targeted delivery to tumor site. The important hallmarks of urological cancers including growth, invasion and angiogenesis can be suppressed by cargo-loaded nanomaterials. Moreover, nanomaterials can improve chemotherapy potential in urological cancer elimination and by providing phototherapy, they mediate synergistic tumor suppression. The clinical application depends on development of biocompatible nanomaterials.

Dimethyl Fumarate Attenuates Pain Behaviors in Osteoarthritis Rats via Induction of Nrf2-Mediated Mitochondrial Biogenesis.

AIMS: Osteoarthritis (OA), a chronic degenerative disease, leads to pain and loss of function. Existing treatments for OA pain have limited efficacy and show significant side effects. Dimethyl fumarate, a robust nuclear factor erythroid 2-related factor 2 (Nrf2) activator, could alleviate pain behaviors in chronic pain. This study aims to investigate the role of dimethyl fumarate in a rat model of OA and its underlying mechanisms. METHODS: We used von Frey filaments to assess the mechanical allodynia. Weight-bearing apparatus was employed to assess the hindlimb weight distribution. Western blot was employed to investigate the protein expressions of mitochondrial biogenesis markers. RT-qPCR was employed to examine the copy number of mitochondrial DNA (mtDNA). RESULTS: Dimethyl fumarate upregulated mechanical paw withdrawal threshold (MIA + Vehicle, 1.6 ± 0.13g [mean ± SEM]; MIA + DMF, 10.5 ± 0.96g; P ＜ 0.0001). Hindlimb weight distribution was alao upregulated by dimethyl fumarate (MIA + Vehicle, 38.17 ± 0.72g; MIA + DMF, 43.59 ± 1.01g; P ＜ 0.01). Besides, activation of Nrf2 remarkably upregulated the protein levels of PGC-1α (MIA + Vehicle, 0.69 ± 0.07; MIA + DMF, 1.08 ± 0.09; P = 0.0037), NRF1 (MIA + Vehicle, 0.69 ± 0.04; MIA + DMF, 1.00 ± 0.11; P = 0.0114), TFAM (MIA + Vehicle, 0.62 ± 0.11; MIA + DMF, 1.02 ± 0.12; P = 0.0147), and the copy number of mtDNA(MIA + Vehicle, 0.52 ± 0.05; MIA + DMF, 3.81 ± 0.21; P ＜ 0.0001) Conclusions: Taken together, these results show that dimethyl fumarate alleviated pain-related behaviors in a rat model of OA through activation of Nrf2-induced mitochondrial biogenesis.

DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation.

BACKGROUND: Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Microglial activation in the spinal cord plays a critical role in the pathogenesis of neuropathic pain. However, the mechanisms underlying spinal microglial activation during neuropathic pain remain incompletely understood. Here, we investigated the role of Dickkopf (DKK) 3 and its interplay with microglial activation in the spinal cord in neuropathic pain. METHODS: In this study, we investigated the effects of intrathecal injection of recombinant DKK3 (rDKK3) on mechanical allodynia and microglial activation in the spinal cord after spared nerve injury (SNI) in rats by western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that SNI induced a significant decrease in the levels of DKK3, Kremen-1 and Dishevelled-1 (DVL-1) and up-regulated the expression of phosphorylated apoptosis signal-regulating kinase 1 (p-ASK1), phosphorylated c-JUN N-terminal kinase (p-JNK), phosphorylated p38 (p-p38) in the spinal cord. Moreover, our results showed that exogenous intrathecal administration of rDKK3 inhibited expression of p-ASK1, p-JNK, p-p38, promoted the transformation of microglia from M1 type to M2 type, and decreased the production of pro-inflammatory cytokines compared to the rats of SNI + Vehicle. However, these effects were reversed by intrathecal administration of Kremen-1 siRNA or Dishevelled-1 (DVL-1) siRNA. CONCLUSIONS: These results suggest that DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation, at least partly, by the Kremen-1 and DVL-1 pathways.

Sestrin2 overexpression attenuates osteoarthritis pain via induction of AMPK/PGC-1α-mediated mitochondrial biogenesis and suppression of neuroinflammation.

BACKGROUND: Our previous study indicated that reactive oxygen species (ROS) are critically involved in chronic pain. Sestrin2 (Sesn2), a novel stress-inducible protein, is evidenced to reduce the generation of ROS. The study examined the role of Sesn2 in osteoarthritis (OA) pain and delineated the underlying molecular mechanisms. METHODS: In the present study, we investigated the impact of Sesn2 on mitochondrial biogenesis in a rat model of OA pain. After adeno-associated viral (AAV)-Sesn2EGFP was injected for 14 days, OA was induced by intra-articular injection of monosodium iodoacetate (MIA). We assessed pain behaviors (weight-bearing asymmetry and paw withdrawal threshold) and explored possible mechanisms in the L4-6 spinal cord. RESULTS: Our results showed that overexpression of Sesn2 in the spinal cord alleviated pain behaviors in OA rats. Moreover, overexpression of Sesn2 increased the activity of AMP-activated protein kinase (AMPK) signaling and significantly restored mitochondrial biogenesis. Besides, Sesn2 overexpression inhibited the activation of astrocytes and microglia, and decreased the production of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the spinal cord of the OA pain rats. These effects were significantly reversed by an AMPK inhibitor. CONCLUSIONS: Collectively, these results suggest that Sesn2 overexpression ameliorates mechanical allodynia and weight-bearing asymmetry in OA rats via activation of AMPK/PGC-1α-mediated mitochondrial biogenesis in the spinal cord. Moreover, Sesn2 overexpression attenuates OA-induced neuroinflammation at least partly by activating AMPK signaling. Sesn2 may become an encouraging therapeutic strategy for OA pain relief and other disorders.

A Neural Circuit from the Paraventricular Thalamus to the Bed Nucleus of the Stria Terminalis for the Regulation of States of Consciousness during Sevoflurane Anesthesia in Mice.

BACKGROUND: The neural circuitry underlying sevoflurane-induced modulation of consciousness is poorly understood. This study hypothesized that the paraventricular thalamus bed nucleus of the stria terminalis pathway plays an important role in regulating states of consciousness during sevoflurane anesthesia. METHODS: Rabies virus-based transsynaptic tracing techniques were employed to reveal the neural pathway from the paraventricular thalamus to the bed nucleus of the stria terminalis. This study investigated the role of this pathway in sevoflurane anesthesia induction, maintenance, and emergence using chemogenetic and optogenetic methods combined with cortical electroencephalogram recordings. Both male and female mice were used in this study. RESULTS: Both γ-aminobutyric acid-mediated and glutamatergic neurons in the bed nucleus of the stria terminalis receive paraventricular thalamus glutamatergic projections. Chemogenetic inhibition of paraventricular thalamus glutamatergic neurons prolonged the sevoflurane anesthesia emergence time (mean ± SD, hM4D-clozapine N-oxide vs. mCherry-clozapine N-oxide, 281 ± 88 vs. 172 ± 48 s, P < 0.001, n = 24) and decreased the induction time (101 ± 32 vs. 136 ± 34 s, P = 0.002, n = 24), as well as the EC5 0 for the loss or recovery of the righting reflex under sevoflurane anesthesia (mean [95% CI] for the concentration at which 50% of the mice lost their righting reflex, 1.16 [1.12 to 1.20] vs. 1.49 [1.46 to 1.53] vol%, P < 0.001, n = 20; and for the concentration at which 50% of the mice recovered their righting reflex, 0.95 [0.86 to 1.03] vs. 1.34 [1.29 to 1.40] vol%, P < 0.001, n = 20). Similar results were observed during suppression of the paraventricular thalamus bed nucleus-stria terminalis pathway. Optogenetic activation of this pathway produced the opposite effects. Additionally, transient stimulation of this pathway efficiently induced behavioral arousal during continuous steady-state general anesthesia with sevoflurane and reduced the depth of anesthesia during sevoflurane-induced burst suppression. CONCLUSIONS: In mice, axonal projections from the paraventricular thalamic neurons to the bed nucleus of the stria terminalis contribute to regulating states of consciousness during sevoflurane anesthesia.

Early Intervention with Autologous Fat Grafting to Reduce Hypertrophic Scar Formation: A Prelimilary Study.

BACKGROUND: Once an early-stage immature scar develops into a hypertrophic scar, it is difficult to achieve satisfactory improvement with existing treatments. Therefore, the prevention of hypertrophic scar formation should be given priority. Fat grafting was previously proven to be an effective treatment for mature scars, but it has not been used in the early-stages of (less than three months) scar formation. OBJECTIVES: We present our experience with the use of combined grafting of macro fat and emulsified fat for prevention of hypertrophic scar formation in patients. METHODS: Thirty-five patients who received fat grafting for facial scar repair were included as a treatment group and another 35 patients without particular interventions were classified as the control group. Patients in both groups were followed up every three months during one year, and the Vancouver Scar Scale (VSS) was used for evaluation of the clinical outcomes at baseline (within one to three months after trauma, burn or surgery) and after 12 months of follow-up. RESULTS: All patients in the treatment group achieved a marked improvement after their first fat grafting procedure. Thirteen patients (37.1%) underwent the second procedure and seven (20%) underwent the third procedure. Statistical analysis of average VSS score also showed significant differences between the treatment and control groups. CONCLUSION: The results of this retrospective study suggest that treatment of immature scars with combined grafting of macro fat and emulsified fat can successfully prevent the formation of hypertrophic scars. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Palladium/Xiao-Phos-Catalyzed Kinetic Resolution of sec-Phosphine Oxides by P-Benzylation.

P-stereogenic tert- and sec-phosphines have wide applications in asymmetric catalysis, materials, and pharmaceutical chemistry, however, their practical synthesis still constitutes a significant challenge. Herein, a successful kinetic resolution of rac-secondary phosphine oxides via the enantioselective P-benzylation process catalyzed by the palladium/Xiao-Phos was designed. Both tert- and sec-phosphine oxides were delivered in good yield and excellent enantiopurity (selectivity factor up to 226.1). The appealing synthetic utilities are further demonstrated by the facile preparation of several valuable P-chiral compounds, precursors of bidentate ligands, as well as transition metal complexes.

Dynamics behind disjunct distribution, hotspot-edge refugia, and discordant RADseq/mtDNA variability: insights from the Emei mustache toad.

BACKGROUND: The distribution of genetic diversity and the underlying processes are important for conservation planning but are unknown for most species and have not been well studied in many regions. In East Asia, the Sichuan Basin and surrounding mountains constitute an understudied region that exhibits a "ring" of high species richness overlapping the eastern edge of the global biodiversity hotspot Mountains of Southwest China. We examine the distributional history and genetic diversification of the Emei mustache toad Leptobrachium boringii, a typical "ring" element characterized by disjunct ranges in the mountains, by integrating time-calibrated gene tree, genetic variability, individual-level clustering, inference of population splitting and mixing from allele frequencies, and paleoclimatic suitability modeling. RESULTS: The results reveal extensive range dynamics, including secondary contact after long-term isolation via westward dispersal accompanied by variability loss. They allow the proposal of a model that combines recurrent contractions caused by Quaternary climatic changes and some failed expansions under suitable conditions for explaining the shared disjunct distribution pattern. Providing exceptional low-elevation habitats in the hotspot area, the eastern edge harbors both long-term refugial and young immigrant populations. This finding and a synthesis of evidence from other taxa demonstrate that a certain contributor to biodiversity, one that preserves and receives low-elevation elements of the east in this case, can be significant for only a particular part of a hotspot. By clarifying the low variability of these refugial populations, we show that discordant mitochondrial estimates of diversity can be obtained for populations that experienced admixture, which would have unlikely left proportional immigrant alleles for each locus. CONCLUSIONS: Dispersal after long-term isolation can explain much of the spatial distribution of genetic diversity in this species, while secondary contact and long-term persistence do not guarantee a large variation. The model for the formation of disjunct ranges may apply to many other taxa isolated in the mountains surrounding the Sichuan Basin. Furthermore, this study provides insights into the heterogeneous nature of hotspots and discordant variability obtained from genome-wide and mitochondrial data.

Climate change and landscape-use patterns influence recent past distribution of giant pandas.

Climate change is one of the most pervasive threats to biodiversity globally, yet the influence of climate relative to other drivers of species depletion and range contraction remain difficult to disentangle. Here, we examine climatic and non-climatic correlates of giant panda (Ailuropoda melanoleuca) distribution using a large-scale 30 year dataset to evaluate whether a changing climate has already influenced panda distribution. We document several climatic patterns, including increasing temperatures, and alterations to seasonal temperature and precipitation. We found that while climatic factors were the most influential predictors of panda distribution, their importance diminished over time, while landscape variables have become relatively more influential. We conclude that the panda's distribution has been influenced by changing climate, but conservation intervention to manage habitat is working to increasingly offset these negative consequences.

Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain.

Paclitaxel-induced neuropathic pain (PINP) is refractory to currently used analgesics. Previous studies show a pivotal role of oxidative stress in PINP. Because the nuclear factor erythroid-2-related factor 2 (Nrf2) has been considered as the critical regulator of endogenous antioxidant defense, we here explored whether activation of Nrf2 could attenuate PINP. A rat model of PINP was established by intraperitoneal injection of paclitaxel (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to assess mechanical allodynia. We showed that a single dose of Nrf2 activator, oltipraz (10, 50, and 100 mg/kg), dose-dependently attenuated established mechanical allodynia, whereas repeated injection of oltipraz (100 mg· kg-1· d-1, i.p. from d 14 to d 18) almost abolished the mechanical allodynia in PINP rats. The antinociceptive effect of oltipraz was blocked by pre-injection of Nrf2 inhibitor trigonelline (20 mg/kg, i.p.). Early treatment with oltipraz (100 mg· kg-1· d-1, i.p. from d 0 to d 6) failed to prevent the development of the PINP, but delayed its onset. Western blot and immunofluorescence analysis revealed that the expression levels of Nrf2 and HO-1 were significantly upregulated in the spinal cord of PINP rats. Repeated injection of oltipraz caused further elevation of the expression levels of Nrf2 and HO-1 in the spinal cord of PINP rats, which was reversed by pre-injection of trigonelline. These results demonstrate that oltipraz ameliorates PINP via activating Nrf2/HO-1-signaling pathway in the spinal cord.

Construction of P-Chiral Alkenylphosphine Oxides through Highly Chemo-, Regio-, and Enantioselective Hydrophosphinylation of Alkynes.

Alkenylphosphine oxides have a wide spectrum of practical applications. However, chemo-, regio-, and enantiocontrolled construction of this structural motif still constitutes a significant synthetic challenge. Here we show that these compounds can be efficiently accessed by using a palladium/Xiao-Phos catalytic system, which leads to the highly regioselective formation of the anti-Markovnikov adducts through addition of a secondary phosphine oxide to an alkyne. Diverse (hetero)aryl and alkyl alkynes, as well as both terminal and internal alkynes can be employed as substrates. The kinetic resolution process makes it possible to produce alkenylphosphine oxide and recovered secondary phosphine oxides with high ee values. Further transformations of these two P-chiral scaffolds confirm the high practicability and application prospect of our synthetic strategies. Initial mechanistic studies strongly suggested that hydropalladation is likely responsible for the conversion process.

P-Chiral Phosphines Enabled by Palladium/Xiao-Phos-Catalyzed Asymmetric P-C Cross-Coupling of Secondary Phosphine Oxides and Aryl Bromides.

The development of transition-metal-catalyzed methods for the synthesis of P-chiral phosphine derivatives poses a considerable challenge. Herein, we present a direct Pd/Xiao-Phos-catalyzed cross-coupling reaction of easily accessible secondary phosphine oxides and aryl bromides, which provides rapid access to P-chiral phosphine oxides. The reaction proceeds efficiently with a wide array of reaction partners to deliver various tertiary phosphine oxides in up to 96% yield and 97% ee. Moreover, the synthesis of DiPAMP ligand and its analogues was also realized, which demonstrates a suitable pathway to switching the branched chain of DiPAMP.

Berberine protects against ischemia-reperfusion injury: A review of evidence from animal models and clinical studies.

Ischemia-reperfusion (I/R) injury is accompanied with high morbidity and mortality and has seriously negative social and economic influences. Unfortunately, few effective therapeutic strategies are available to improve its outcome. Berberine is a natural medicine possessing multiple beneficial biological activities. Emerging evidence indicates that berberine has potential protective effects against I/R injury in brain, heart, kidney, liver, intestine and testis. However, up-to-date review focusing on the beneficial role of berberine against I/R injury is not yet available. In this paper, results from animal models and clinical studies are concisely presented and its mechanisms are discussed. We found that berberine ameliorates I/R injury in animal models via its anti-oxidant, anti-apoptotic and anti-inflammatory effects. Moreover, berberine also attenuates I/R injury by suppressing endoplasmic reticulum stress and promoting autophagy. Additionally, regulation of periphery immune system may also contributes to the beneficial effect of berberine against I/R injury. Although clinical evidence is limited, the current studies indicate that berberine may attenuate I/R injury via inhibiting excessive inflammatory response in patients. Collectively, berberine might be used as an alternative therapeutic strategy for the management of I/R injury.

Preparation and characterization of a new open-tubular capillary column for enantioseparation by capillary electrochromatography.

In order to use the enantioseparation capability of cationic cyclodextrin and to combine the advantages of capillary electrochromatography (CEC) with open-tubular (OT) column, in this study, a new OT-CEC, coated with cationic cyclodextrin (1-allylimidazolium-ß-cyclodextrin [AI-ß-CD]) as chiral stationary phase (CSP), was prepared and applied for enantioseparation. Synthesized AI-ß-CD was characterized by infrared (IR) spectrometry and mass spectrometry (MS). The preparation conditions for the AI-ß-CD-coated column were optimized with the orthogonal experiment design L9 (34 ). The column prepared was characterized by scanning electron microscopy (SEM) and elemental analysis (EA). The results showed that the thickness of stationary phase in the inner surface of the AI-ß-CD-coated columns was about 0.2 to 0.5 µm. The AI-ß-CD content in stationary phase based on the EA was approximately 2.77 mmol·m-2 . The AI-ß-CD-coated columns could separate all 14 chiral compounds (histidine, lysine, arginine, glutamate, aspartic acid, cysteine, serine, valine, isoleucine, phenylalanine, salbutamol, atenolol, ibuprofen, and napropamide) successfully in the study and exhibit excellent reproducibility and stability. We propose that the column, coated with AI-ß-CD, has a great potential for enantioseparation in OT-CEC.