Phylogenetic evidence clarifies the history of the extrusion of Indochina.

The southeastward extrusion of Indochina along the Ailao Shan-Red River shear zone (ARSZ) is one of two of the most prominent consequences of the India-Asia collision. This plate-scale extrusion has greatly changed Southeast Asian topography and drainage patterns and effected regional climate and biotic evolution. However, little is known about how Indochina was extruded toward the southeast over time. Here, we sampled 42 plant and animal clades (together encompassing 1,721 species) that are distributed across the ARSZ and are not expected to disperse across long distances. We first assess the possible role of climate on driving the phylogenetic separations observed across the ARSZ. We then investigate the temporal dynamics of the extrusion of Indochina through a multitaxon analysis. We show that the lineage divergences across the ARSZ were most likely associated with the Indochinese extrusion rather than climatic events. The lineage divergences began at ~53 Ma and increased sharply ~35 Ma, with two peaks at ~19 Ma and ~7 Ma, and one valley at ~13 Ma. Our results suggest a two-phase model for the extrusion of Indochina, and in each phase, the extrusion was subject to periods of acceleration and decrease, in agreement with the changes of the India-Asia convergence rate and angle from the early Eocene to the late Miocene. This study highlights that a multitaxon analysis can illuminate the timing of subtle historical events that may be difficult for geological data to pinpoint and can be used to explore other tectonic events.

Biotic colonization of subtropical East Asian caves through time.

Caves are home to unique and fragile biotas with high levels of endemism. However, little is known about how the biotic colonization of caves has developed over time, especially in caves from middle and low latitudes. Subtropical East Asia holds the world's largest karst landform with numerous ancient caves, which harbor a high diversity of cave-dwelling organisms and are regarded as a biodiversity hotspot. Here, we assess the temporal dynamics of biotic colonization of subtropical East Asian caves through a multi-taxon analysis with representatives of green plants, animals, and fungi. We then investigate the consequences of paleonviromental changes on the colonization dynamics of these caves in combination with reconstructions of vegetation, temperature, and precipitation. We discover that 88% of cave colonization events occurred after the Oligocene-Miocene boundary, and organisms from the surrounding forest were a major source for subtropical East Asian cave biodiversity. Biotic colonization of subtropical East Asian caves during the Neogene was subject to periods of acceleration and decrease, in conjunction with large-scale, seasonal climatic changes and evolution of local forests. This study highlights the long-term evolutionary interaction between surface and cave biotas; our climate-vegetation-relict model proposed for the subtropical East Asian cave biota may help explain the evolutionary origins of other mid-latitude subterranean biotas.

Metal Clusters Based Multifunctional Materials for Solar Cells.

As a multifunctional material, metal clusters have recently received some attention for their application in solar cells.This review delves into the multifaceted role of metal clusters in advancing solar cell technologies, covering diverse aspects from electron transport and interface modification to serving as molecular precursors for inorganic materials and acting as photosensitizers in metal-cluster sensitized solar cells (MCSSCs). The studies conducted by various researchers illustrate the crucial impact of metal clusters, such as gold nanoclusters (Au NCs), on enhancing solar cell efficiency through size-dependent effects, distinct interface behaviors, and tailored interface engineering. From optimizing charge transfer rates to improving light absorption and reducing carrier recombination, metal clusters prove instrumental in shaping the landscape of solar energy conversion.The promising performance of metal-cluster sensitized solar cells, coupled with their scalability and flexibility, positions them as a exciting avenue for future clean energy applications. The article concludes by emphasizing the need for continued interdisciplinary research and technological innovation to unlock the full potential of metal clusters in contributing to sustainable and high-performance solar cells.

Plastome Evolution, Phylogenomics, and DNA Barcoding Investigation of Gastrochilus (Aeridinae, Orchidaceae), with a Focus on the Systematic Position of Haraella retrocalla.

Gastrochilus is an orchid genus containing about 70 species in tropical and subtropical Asia with high morphological diversity. The phylogenetic relationships among this genus have not been fully resolved, and the plastome evolution has not been investigated either. In this study, five plastomes of Gastrochilus were newly reported, and sixteen plastomes of Gastrochilus were used to conduct comparative and phylogenetic analyses. Our results showed that the Gastrochilus plastomes ranged from 146,183 to 148,666 bp, with a GC content of 36.7-36.9%. There were 120 genes annotated, consisting of 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. No contraction and expansion of IR borders, gene rearrangements, or inversions were detected. Additionally, the repeat sequences and codon usage bias of Gastrochilus plastomes were highly conserved. Twenty hypervariable regions were selected as potential DNA barcodes. The phylogenetic relationships within Gastrochilus were well resolved based on the whole plastome, especially among main clades. Furthermore, both molecular and morphological data strongly supported Haraella retrocalla as a member of Gastrochilus (G. retrocallus).

[Study on mechanism of inhibiting proliferation of head and neck cancer cells by citral, active ingredient of lemon essential oil].

To explore the active substances exerting anti-tumour effect in lemon essential oil and the molecular mechanism inhibiting the proliferation of head and neck cancer cells SCC15 and CAL33, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay(MTT) was utilized to identify the active component inhibiting the proliferation of head and neck cancer cells, namely citral. The IC_(50) of citral inhibiting the proliferation of head and neck cancer cells and normal cells were also determined. In addition, a 5-ethynyl-2'-deoxyuridine(EdU) staining assay was used to detect the effect of citral on the proliferation rate of head and neck cancer cells, and a colony formation assay was used to detect the effect of citral on tumor sphere formation of head and neck cancer cells in vitro. The cell cycle arrest and apoptosis induction of head and neck cancer cells by citral were evaluated by flow cytometry, and Western blot was used to detect the effect of citral on the expression levels of cell cycle-and apoptosis-related proteins in head and neck cancer cells. The findings indicated that citral could effectively inhibit the proliferation and growth of head and neck cancer cells, with anti-tumor activity, and its half inhibitory concentrations for CAL33 and SCC15 were 54.78 and 25.23 µg·mL~(-1), respectively. Furthermore, citral arrested cell cycle at G_2/M phase by down-regulating cell cycle-related proteins such as S-phase kinase associated protein 2(SKP2), C-MYC, cyclin dependent kinase 1(CDK1), and cyclin B. Moreover, citral increased the cysteinyl aspartate-specific proteinase-3(caspase-3), cysteinyl aspartate-specific proteinase-9(caspase-9), and cleaved poly ADP-ribose polymerase(PARP). It up-regulated the level of autophagy-related proteins including microtubule associated protein 1 light chain 3B(LC3B), sequestosome 1(P62/SQSTM1), autophagy effector protein Beclin1(Beclin1), and lysosome-associate membrane protein 1(LAMP1), suggesting that citral could effectively trigger cell apoptosis and cell autophagy in head and neck cancer cells. Furthermore, the dual-tagged plasmid system mCherry-GFP-LC3 was used, and it was found that citral impeded the fusion of autophagosomes and lysosomes, leading to autophagic flux blockage. Collectively, our findings reveal that the main active anti-proliferation component of lemon essential oil is citral, and this component has a significant inhibitory effect on head and neck cancer cells. Its underlying molecular mechanism is that citral induces apoptosis and autophagy by cell cycle arrest and ultimately inhibits cell proliferation.

Plastome phylogenomics and morphological traits analyses provide new insights into the phylogenetic position, species delimitation and speciation of Triplostegia (Caprifoliaceae).

BACKGROUND: The genus Triplostegia contains two recognized species, T. glandulifera and T. grandiflora, but its phylogenetic position and species delimitation remain controversial. In this study, we assembled plastid genomes and nuclear ribosomal DNA (nrDNA) cistrons sampled from 22 wild Triplostegia individuals, each from a separate population, and examined these with 11 recently published Triplostegia plastomes. Morphological traits were measured from herbarium specimens and wild material, and ecological niche models were constructed. RESULTS: Triplostegia is a monophyletic genus within the subfamily Dipsacoideae comprising three monophyletic species, T. glandulifera, T. grandiflora, and an unrecognized species Triplostegia sp. A, which occupies much higher altitude than the other two. The new species had previously been misidentified as T. glandulifera, but differs in taproot, leaf, and other characters. Triplotegia is an old genus, with stem age 39.96 Ma, and within it T. glandulifera diverged 7.94 Ma. Triplostegia grandiflora and sp. A diverged 1.05 Ma, perhaps in response to Quaternary climate fluctuations. Niche overlap between Triplostegia species was positively correlated with their phylogenetic relatedness. CONCLUSIONS: Our results provide new insights into the species delimitation of Triplostegia, and indicate that a taxonomic revision of Triplostegia is needed. We also identified that either rpoB-trnC or ycf1 could serve as a DNA barcode for Triplostegia.

Phylogenomic insights into the origin and evolutionary history of evergreen broadleaved forests in East Asia under Cenozoic climate change.

The evergreen versus deciduous leaf habit is an important functional trait for adaptation of forest trees and has been hypothesized to be related to the evolutionary processes of the component species under paleoclimatic change, and potentially reflected in the dynamic history of evergreen broadleaved forests (EBLFs) in East Asia. However, knowledge about the shift of evergreen versus deciduous leaf with the impact of paleoclimatic change using genomic data remains rare. Here, we focus on the Litsea complex (Lauraceae), a key lineage with dominant species of EBLFs, to gain insights into how evergreen versus deciduous trait shifted, providing insights into the origin and historical dynamics of EBLFs in East Asia under Cenozoic climate change. We reconstructed a robust phylogeny of the Litsea complex using genome-wide single-nucleotide variants (SNVs) with eight clades resolved. Fossil-calibrated analyses, diversification rate shifts, ancestral habit, ecological niche modelling and climate niche reconstruction were employed to estimate its origin and diversification pattern. Taking into account studies on other plant lineages dominating EBLFs of East Asia, it was revealed that the prototype of EBLFs in East Asia probably emerged in the Early Eocene (55-50 million years ago [Ma]), facilitated by the greenhouse warming. As a response to the cooling and drying climate in the Middle to Late Eocene (48-38 Ma), deciduous habits were evolved in the dominant lineages of the EBLFs in East Asia. Up to the Early Miocene (23 Ma), the prevailing of East Asian monsoon increased the extreme seasonal precipitation and accelerated the emergence of evergreen habits of the dominant lineages, and ultimately shaped the vegetation resembling that of today.

Species richness disparity in tropical terrestrial herbaceous floras: Evolutionary insight from Collabieae (Orchidaceae).

Species richness is spatially heterogeneous even in the hyperdiverse tropical floras. The main cause of uneven species richness among the four tropical regions are hot debated. To date, higher net diversification rates and/or longer colonization time have been usually proposed to contribute to this pattern. However, there are few studies to clarify the species richness patterns in tropical terrestrial floras. The terrestrial tribe Collabieae (Orchidaceae) unevenly distributes in the tropical regions with a diverse and endemic center in Asia. Twenty-one genera 127 species of Collabieae and 26 DNA regions were used to reconstruct the phylogeny and infer the biogeographical processes. We compared the topologies, diversification rates and niche evolutionary rates of Collabieae and regional lineages on empirical samplings and different simulated samplings fractions respectively. Our results suggested that the Collabieae originated in Asia at the earliest Oligocene, and then independently spread to Africa, Central America, and Oceania since the Miocene via long-distance dispersal. These results based on empirical data and simulated data were similar. BAMM, GeoSSE and niche analyses inferred that the Asian lineages had higher net diversification and niche evolutionary rates than those of Oceanian and African lineages on the empirical and simulated analyses. Precipitation is the most important factor for Collabieae, and the Asian lineage has experienced more stable and humid climate, which may promote the higher net diversification rate. Besides, the longer colonization time may also be associated with the Asian lineages' diversity. These findings provided a better understanding of the regional diversity heterogeneity in tropical terrestrial herbaceous floras.

A magnetic resonance imaging-based decision-making tool for predicting complex anal fistulas healing in the early postoperative period.

BACKGROUND: Magnetic resonance imaging (MRI) has excellent accuracy in diagnosing preoperative lesions before anal fistula surgery. However, MRI is not good in identifying early recurrent lesions and effective methods for quantitative assessment of fistula healing are still warranted. This retrospective study aimed to develop and validate a specific MRI-based nomogram model to predict fistula healing during the early postoperative period. METHODS: Patients with complex cryptoglandular anal fistulas who underwent surgery between January 2017 and October 2020 were included in this study. MRI features and clinical parameters were analyzed using univariate and multivariate logistic regression analysis. A nomogram for predicting fistula healing was constructed and validated. RESULTS: In total, 200 patients were included, of whom 186 (93%) were male, with a median age of 36 (18-65) years. Of the fistulas, 58.5% were classified as transsphincteric and 19.5% as suprasphincteric. The data were randomly divided into the training cohort and testing cohort at a ratio of 7:3. Logistic analysis revealed that CNR, ADC, alcohol intake history, and suprasphincteric fistula were significantly correlated with fistula healing. These four predictors were used to construct a predictive nomogram model in the training cohort. AUC was 0.880 and 0.847 for the training and testing cohorts, respectively. Moreover, the decision and calibration curves showed high coherence between the predicted and actual probabilities of fistula healing. CONCLUSIONS: We developed a predictive model and constructed a nomogram to predict fistula healing during the early postoperative period. This model showed good performance and may be clinically utilized for the management of anal fistulas.

Mesenchymal stem cells in fibrotic diseases-the two sides of the same coin.

Fibrosis is caused by extensive deposition of extracellular matrix (ECM) components, which play a crucial role in injury repair. Fibrosis attributes to ~45% of all deaths worldwide. The molecular pathology of different fibrotic diseases varies, and a number of bioactive factors are involved in the pathogenic process. Mesenchymal stem cells (MSCs) are a type of multipotent stem cells that have promising therapeutic effects in the treatment of different diseases. Current updates of fibrotic pathogenesis reveal that residential MSCs may differentiate into myofibroblasts which lead to the fibrosis development. However, preclinical and clinical trials with autologous or allogeneic MSCs infusion demonstrate that MSCs can relieve the fibrotic diseases by modulating inflammation, regenerating damaged tissues, remodeling the ECMs, and modulating the death of stressed cells after implantation. A variety of animal models were developed to study the mechanisms behind different fibrotic tissues and test the preclinical efficacy of MSC therapy in these diseases. Furthermore, MSCs have been used for treating liver cirrhosis and pulmonary fibrosis patients in several clinical trials, leading to satisfactory clinical efficacy without severe adverse events. This review discusses the two opposite roles of residential MSCs and external MSCs in fibrotic diseases, and summarizes the current perspective of therapeutic mechanism of MSCs in fibrosis, through both laboratory study and clinical trials.

PARP in colorectal cancer: Molecular mechanisms, immunity, clinical trials, and drug combinations.

The changes in cell homeostasis in the tumor microenvironment may affect the development of colorectal cancer (CRC). Genomic instability is an important factor. Persistent genomic instability leads to epigenetic changes, and mutations are a major factor in the progression of CRC. Based on these mechanisms, it is reasonable to link poly (ADP-ribose) polymerase (PARP) with the treatment of CRC. PARP is mainly involved in DNA repair, which has an essential role in the DNA damage response and prevention of DNA damage, and maintains oxidation and superoxide redox homeostasis in the intracellular environment of the tumor. This article reviews the latest research progress on PARP and PARP inhibitors (PARPi) in CRC. It mainly includes molecular mechanisms, immunity, clinical trials, and combination strategies of CRC. The research of PARPi in CRC has broad prospects, and the combinations with other drugs are the main research direction in the future.

An Efficient CRT Based Algorithm for Frequency Determination from Undersampled Real Waveform.

The Chinese Remainder Theorem (CRT) based frequency estimation has been widely studied during the past two decades. It enables one to estimate frequencies by sub-Nyquist sampling rates, which reduces the cost of hardware in a sensor network. Several studies have been done on the complex waveform; however, few works studied its applications in the real waveform case. Different from the complex waveform, existing CRT methods cannot be straightforwardly applied to handle a real waveform's spectrum due to the spurious peaks. To tackle the ambiguity problem, in this paper, we propose the first polynomial-time closed-form Robust CRT (RCRT) for the single-tone real waveform, which can be considered as a special case of RCRT for arbitrary two numbers. The time complexity of the proposed algorithm is O(L), where L is the number of samplers. Furthermore, our algorithm also matches the optimal error-tolerance bound.

Value of angiographic regional circulation signs in predicting hemorrhagic transformation after endovascular thrombectomy.

OBJECTIVE: The aim of this study was to evaluate the predictive value of the early venous filling (EVF) sign, the basal ganglia blush (BGB) sign and both the EVF and BGB signs for the hemorrhagic transformation (HT) and parenchymal hematoma (PH) in patients after endovascular thrombectomy. METHODS: This study included patients with anterior circulation large vessel occlusive stroke treated with endovascular thrombectomy from May 2017 to December 2021. The predictive value of regional circulation signs for HT and PH were assessed using logistic regression models adjusted for confounders, and further a multiplicative interaction term was added to investigate the effect of different stroke severity on its predictive value. RESULTS: Among the 350 patients included and after adjusting for confounders, those with the EVF sign (adjusted OR=3.934, 95% CI:2.326-6.655), the BGB sign (adjusted OR=3.776, 95% CI:2.341-6.089), and both the EVF and BGB signs (adjusted OR=3.250, 95% CI: 1.886-5.600) were more likely to have HT. The EVF sign (adjusted OR=3.545, 95% CI:2.036-6.170), the BGB sign (adjusted OR=3.742, 95% CI:2.110-6.639), and both the EVF and BGB signs (adjusted OR=3.139, 95% CI: 1.776-5.549) were also significantly correlated with PH. When stratified according to stroke severity, we further found there were significant interactions between regional circulation signs and stroke severity on postoperative HT and PH (all P for interaction < 0.001). CONCLUSIONS: Regional circulation signs were independently associated with HT and PH after endovascular thrombectomy and had a higher predictive value in patients with severe stroke compared with mild to moderate stroke.

Porphyrin Supramolecule as Surface Carrier Modulator Imparts Hole Transporter with Enhanced Mobility for Perovskite Photovoltaics.

Modulating the surface charge transport behavior of hole transport materials (HTMs) would be as an potential approach to improve their hole mobility, while yet realized for fabricating efficient photovoltaic devices. Here, an oxygen bridged dimer-based monoamine FeIII porphyrin supramolecule is prepared and doped in HTM film. Theoretical analyses reveal that the polaron distributed on dimer can be coupled with the parallel arranged polarons on adjacent dimers. This polaron coupling at the interface of supramolecule and HTM can resonates with hole flux to increase hole transport efficiency. Mobility tests reveal that the hole mobility of doped HTM film is improved by 8-fold. Doped perovskite device exhibits an increased efficiency from 19.8 % to 23.2 %, and greatly improved stability. This work provides a new strategy to improve the mobility of HTMs by surface carrier modulation, therefore fabricating efficient photovoltaic devices.

Directional Defect Management in Perovskites by In Situ Decomposition of Organic Metal Chalcogenides for Efficient Solar Cells.

Directional defects management in polycrystalline perovskite film with inorganic passivator is highly demanded while yet realized for fabricating efficient and stable perovskite solar cells (PSCs). Here, we develop a directional passivation strategy employing a two-dimensional (2D) material, Cu-(4-mercaptophenol) (Cu-HBT), as a passivator precursor. Cu-HBT combines the merits of the targeted modification from organic passivator and excellent stability offered by inorganic passivator. Featuring with dense organic functional motifs on its surfaces, Cu-HBT has the capability to "find" and fasten to the Pb defect sites in perovskites through coordination interactions during a spin-coating process. During subsequent annealing treatment, the organic functional motifs cleave from Cu-HBT and convert in situ into p-type semiconductors, Cu2 S and PbS. The resultant Cu2 S and PbS not only serve as stable inorganic passivators on the perovskite surface, significantly enhancing cell stability, but also facilitate efficient charge extraction and transport, resulting in an impressive efficiency of up to 23.5 %. This work contributes a new defect management strategy by directionally yielding the stable inorganic passivators for highly efficient and stable PSCs.

Directional Transformation of Heterometallic Oxo Clusters: A New Approach to Prepare Wide-Bandgap Cathode Interlayers for Perovskite Solar Cells.

Typical wide-band gap cathode interlayer materials are difficulty in reducing interface recombination without limiting charge transport in perovskite solar cells (PSCs). Here, a lead-doped titanium-oxo cluster protected by S-containing ligands is introduced at the interface of perovskite and SnO2 . By in situ heating, the cluster is transformed into PbSO4 -PbTi3 O7 heterostructure. The oxygen atoms from sulfate ion in heterostructure connect with iodine from perovskite to boost interfacial electron extraction and reduce charge recombination. While the yielded metallic interface between PbSO4 and PbTi3 O7 promotes the electron transport across the interface. Finally, an efficiency as high as 24.2 % for the modified PSC is obtained. The heterostructure well-stabilize the interface of perovskite and SnO2 , to greatly improve the device stability. This work provides a novel strategy to prepare wide-band gap cathode interlayer by directional transformation of heterometallic oxo clusters.

Immigration dynamics of tropical and subtropical Southeast Asian limestone karst floras.

Ex situ origins and dispersal of taxa have played important roles in the assembly of island-like biodiversity hotspots. Insular limestone karsts in Southeast Asia are hotspots of biodiversity and endemism, but the immigration processes of their unique floras are still poorly known. Here, we used Gesneriaceae as a proxy to investigate the immigration dynamics of tropical and subtropical Southeast Asian karst floras. We present the most comprehensive phylogenetic analysis of the Old World gesneriads to date based on twelve loci. By estimating divergence times and reconstructing ancestral states (habitat, soil type and range), we found that immigration into subtropical Southeast Asian karst floras first occurred in the Early Miocene, with two peaks in the Early-Middle Miocene and the Pliocene-Early Pleistocene, whereas immigration into tropical Southeast Asian karsts initiated in the Late Eocene, with two peaks in the Late Oligocene and the Late Miocene. We also discover that Southeast Asian karst biodiversity comprises immigrant pre-adapted lineages and descendants from local acid soil ancestors, although niche shift from acid soil to karst in tropical Southeast Asian islands was lacking. This study advances our understanding of the historical assembly of Southeast Asian karst floras.

Influences of different referral modes on clinical outcomes after endovascular therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: As endovascular thrombectomy (EVT) is time-dependent, it is crucial to refer patients promptly. Current referral modes include Mothership (MS), Drip and Ship (DS) and Drive the Doctor (DD). The purpose of this study was to investigate the influences of different referral modes on the clinical outcomes of patients with acute ischemic stroke after EVT.  METHODS: A total of 349 patients from 15 hospitals between April 2017 and March 2020 were enrolled. The primary outcomes include poor outcome (modified Rankin Scale score of 3 to 6), symptomatic intracranial hemorrhage transformation (sICH), mortality and cost. Regression analysis was used to assess the association of referral modes with poor outcome, sICH, mortality and cost in acute ischemic stroke patients. RESULTS: Among the 349 patients, 83 were in DD group (23.78%), 85 in MS group (24.36%) and 181 in DS group (51.86%). There were statistically significant differences in intravenous thrombolysis, onset-to-door time, onset-to-puncture time, puncture-to-recanalization time, door-to-puncture time, door-to-recanalization time, and cost among the DD, MS, and DS groups (59.04% vs 35.29% vs 33.15%, P<0.001; 90 vs 166 vs 170 minutes, P<0.001; 230 vs 270 vs 270 minutes, P<0.001; 82 vs 54 vs 51 minutes, P<0.001; 110 vs 85 vs 96 minutes, P=0.004; 210 vs 146 vs 150 minutes, P<0.001; 64258 vs 80041 vs 70750 Chinese Yuan, P=0.018). In terms of sICH, mortality and poor outcome, there was no significant difference among the DD, MS, and DS groups (22.89% vs 18.82% vs 19.34%, P=0.758; 24.10% vs 24.71% vs 29.83%, P=0.521; 64.47% vs 64.71% vs 68.51%, P=0.827). The results of multiple regression analysis indicated that there was no independent correlation between different referral modes regarding sICH (ORMS: 0.50, 95%CI: 0.18, 1.38, P=0.1830; ORDS: 0.47, 95%CI: 0.19, 1.16, P=0.1000), mortality (ORMS: 0.56, 95%CI: 0.19, 1.67, P=0.2993; ORDS: 0.65, 95%CI: 0.25, 1.69, P=0.3744) and poor outcome (ORMS: 0.61, 95%CI: 0.25, 1.47, P=0.2705; ORDS: 0.53, 95%CI: 0.24, 1.18, P=0.1223). However, there was a correlation between MS group and cost (ß=30449.73, 95%CI: 11022.18, 49877.29; P=0.0023). The multiple regression analysis on patients finally admitted in comprehensive stroke center (MS+DS) versus patients finally admitted in primary stroke center (DD) showed that DD mode was independently associated with lower costs (ß=-19438.86, 95%CI: -35977.79, -2899.94; P=0.0219). CONCLUSION: There was no independent correlation between three referral modes and sICH, mortality, poor outcome correspondingly. Different referral modes can be implemented in clinical practice according to the situations encountered. Compared to MS and DS modes, DD mode is more economical.

Stratifin promotes renal dysfunction in ischemic and nephrotoxic AKI mouse models via enhancing RIPK3-mediated necroptosis.

Stratifin (SFN) is a member of the 14-3-3 family of highly conserved soluble acidic proteins, which regulates a variety of cellular activities such as cell cycle, cell growth and development, cell survival and death, and gene transcription. Acute kidney injury (AKI) is prevalent disorder characterized by inflammatory response, oxidative stress, and programmed cell death in renal tubular epithelial cells, but there is still a lack of effective therapeutic target for AKI. In this study, we investigated the role of SFN in AKI and the underlying mechanisms. We established ischemic and nephrotoxic AKI mouse models caused by ischemia-reperfusion (I/R) and cisplatin, respectively. We conducted proteomic and immunohistochemical analyses and found that SFN expression levels were significantly increased in AKI patients, cisplatin- or I/R-induced AKI mice. In cisplatin- or hypoxia/reoxygenation (H/R)-treated human proximal tubule epithelial cells (HK2), we showed that knockdown of SFN significantly reduced the expression of kidney injury marker Kim-1, attenuated programmed cell death and inflammatory response. Knockdown of SFN also significantly alleviated the decline of renal function and histological damage in cisplatin-caused AKI mice in vivo. We further revealed that SFN bound to RIPK3, a key signaling modulator in necroptosis, to induce necroptosis and the subsequent inflammation in cisplatin- or H/R-treated HK2 cells. Overexpression of SFN increased Kim-1 protein levels in cisplatin-treated MTEC cells, which was suppressed by RIPK3 knockout. Taken together, our results demonstrate that SFN that enhances cisplatin- or I/R-caused programmed cell death and inflammation via interacting with RIPK3 may serve as a promising therapeutic target for AKI treatment.

Osteopontin and its downstream carcinogenic molecules: regulatory mechanisms and prognostic value in cancer progression.

Osteopontin (OPN) is a multifunctional phosphorylated glycoprotein that is expressed at significantly elevated levels in various cancers. OPN overexpression is closely associated with the development of cancer progression such as proliferation, metastasis, angiogenesis, apoptosis resistance, drug resistance, and immunosuppression, and may also be an independent prognostic biomarker for a variety of cancers. This review broadly summarizes the mechanisms that regulate the expression of downstream oncogenic molecules after OPN binds to integrin receptors or CD44 receptors, which involve a complex intracellular "signaling traffic network" (including key kinases, signaling pathways, and transcription factors). In addition, we review the prognostic value of OPN, OPN synergistic downstream oncogenic molecules in the female breast, non-small cell lung, prostate, colorectal, gastric, and hepatocellular carcinomas. The prognostic value of OPN in tissues or blood may vary due to differences in study subjects or detection methods, and this aspect of the study requires further systematization with a view to applying the detection of OPN to clinical applications. Importantly, based on the fact that the oncogenic effect of OPN correlates with the expression of the above-mentioned oncogenic molecules, this work may provide some help in the study of combination therapy targeting OPN and the above-mentioned oncogenic molecules.