Antibacterial activity of t-cinnamaldehyde: An approach to its mechanistic principle towards enterohemorrhagic Escherichia coli (EHEC).

BACKGROUND: Compounds of natural origin are potent source of drugs with unique mechanisms of action. Among phytochemicals, trans-cinnamaldehyde (t-CA) exhibits a wide range of biological activity, thus has been used for centuries to fight bacterial and fungal infections. However, the molecular basis of these properties has not been fully covered. Considering that difficult-to-control infections are becoming a rising global problem, there is a need to elucidate the molecular potential of t-CA. PURPOSE: To evaluate the antibacterial activity of t-CA against Shiga-toxigenic E. coli strains and elucidate its mechanism of action based on the inhibition of the virulence factor expression. METHODS: The antimicrobial potential of t-CA was assessed with two-fold microdilution and time-kill assays. Further evaluation included bioluminescence suppression assays, quantification of reactive oxygen species (ROS) and assessment of NAD+/NADH ratios. Morphological changes post t-CA exposure were examined using transmission electron microscopy. RNA sequencing and radiolabeling of nucleotides elucidated the metabolic alterations induced by t-CA. Toxin expression level was monitored through the application of fusion proteins, monitoring of bacteriophage development, and fluorescence microscopy studies. Lastly, the therapeutic efficacy in vivo was assessed using Galleria mellonella infection model. RESULTS: A comprehensive study of t-CA's bioactivity showed unique properties affecting bacterial metabolism and morphology, resulting in significant bacterial cell deformation and effective virulence inhibition. Elucidation of the underlying mechanisms indicated that t-CA activates the global regulatory system, the stringent response, manifested by its alarmone, (p)ppGpp, overproduction mediated by the RelA enzyme, thereby inhibiting bacterial proliferation. Intriguingly, t-CA effectively downregulates Shiga toxin gene expression via alarmone molecules, indicating its potential for therapeutic effect. In vivo validation demonstrated a significant improvement in larval survival rates post- t-CA treatment with 50 mg/kg (p < 0.05), akin to the efficacy observed with azithromycin, thus indicating its effectiveness against EHEC infections (p < 0.05). CONCLUSIONS: Collectively, these results reveal the robust antibacterial capabilities of t-CA, warranting its further exploration as a viable anti-infective agent.

Biomimetic Superstructured Interphase for Aqueous Zinc-Ion Batteries.

The practical application of aqueous zinc-ion batteries (AZIBs) is greatly challenged by rampant dendrites and pestilent side reactions resulting from an unstable Zn-electrolyte interphase. Herein, we report the construction of a reliable superstructured solid electrolyte interphase for stable Zn anodes by using mesoporous polydopamine (2D-mPDA) platelets as building blocks. The interphase shows a biomimetic nacre's "brick-and-mortar" structure and artificial transmembrane channels of hexagonally ordered mesopores in the plane, overcoming the mechanical robustness and ionic conductivity trade-off. Experimental results and simulations reveal that the -OH and -NH groups on the surface of artificial ion channels can promote rapid desolvation kinetics and serve as an ion sieve to homogenize the Zn2+ flux, thus inhibiting side reactions and ensuring uniform Zn deposition without dendrites. The 2D-mPDA@Zn electrode achieves an ultralow nucleation potential of 35 mV and maintains a Coulombic efficiency of 99.8% over 1500 cycles at 5 mA cm-2. Moreover, the symmetric battery exhibits a prolonged lifespan of over 580 h at a high current density of 20 mA cm-2. This biomimetic superstructured interphase also demonstrates the high feasibility in Zn//VO2 full cells and paves a new route for rechargeable aqueous metal-ion batteries.

Micelles Cascade Assembly to Tandem Porous Catalyst for Waste Plastics Upcycling.

Catalytic upcycling of polyolefins into high-value chemicals represents the direction in end-of-life plastics valorization, but poses great challenges. Here, we report the synthesis of a tandem porous catalyst via a micelle cascade assembly strategy for selectively catalytic cracking of polyethylene into olefins at a low temperature. A hierarchically porous silica layer from mesopore to macropore is constructed on the surface of microporous ZSM-5 nanosheets through cascade assembly of dynamic micelles. The outer macropore arrays can adsorb bulky polyolefins quickly by the capillary and hydrophobic effects, enhancing the diffusion and access to active sites. The middle mesopores present a nanoconfinement space, pre-cracking polyolefins into intermediates by weak acid sites, which then transport into zeolites micropores for further cracking by strong Brønsted acid sites. The hierarchically porous and acidic structures, mimicking biomimetic protease catalytic clefts, ideally match the tandem cracking steps of polyolefins, thus suppressing coke formation and facilitating product escape. As a result, light hydrocarbons (C1-C7) are produced with a yield of 443 mmol gZSM-5 -1, where 74.3 % of them are C3-C6 olefins, much superior to ZSM-5 and porous silica catalysts. This tandem porous catalyst exemplifies a superstructure design of catalytic cracking catalysts for industrial and economical upcycling of plastic wastes.

Establishment and application of an indirect ELISA for Getah virus E2 antibody detection.

Getah virus (GETV) is a mosquito-transmitted disease that affects animals, causing fever, aseptic meningitis, and abortion. Its prevalence in China poses risks to both animal health and public well-being. Currently, there is a scarcity of seroepidemiological data on GETV due to the absence of commercial antibody detection kits for pigs. The aim of this study is to develop a rapid, accurate, and sensitive ELISA, providing a reliable tool for GETV seroepidemiology and laying the foundation for future commercial assay development. In this study, we removed specific hydrophobic domains and intracellular structures from E2 proteins and constructed the recombinant plasmid pCold-TF-E2. The recombinant protein was expressed using a prokaryotic expression system, and efficient purification of the rE2 protein was achieved using a nickel affinity column. The purified rE2 protein is suitable for the development of an indirect ELISA (rE2 ELISA). Following the optimization of reaction conditions for the rE2-ELISA, the cut-off value was 0.356. Additionally, the rE2-ELISA method showed a positive rate of 37.1% for IgG antibodies against GETV when testing 986 pig clinical serum samples collected from pigs in Sichuan between May 2022 and September 2022. The rE2-ELISA method displayed a 95.1% overall agreement with VNT, boasting a sensitivity of 98.2% and a specificity of 92.6%. These results indicate that IgG ELISA based on rE2 protein is an efficient and economical method for the detection of GETV antibodies in pigs, facilitating the diagnosis and prevention of GETV.

Identification and interruption of inheritance of familial cryptic translocations: A case report.

BACKGROUND: Cryptic translocations can be identified via genetic analysis of aborted tissues or malformed infants, but it is difficult to deduce the parental origins of the translocations. In the absence of such information, it is not easy to distinguish translocations from normal embryos during pre-implantation genetic testing, that seeks to block familial transmission of translocations. METHODS: Here, we present a new method that detects cryptic translocations and blocks familial transmission thereof. Whole-genome, low-coverage mate-pair sequencing (WGLMPS) revealed chromosome breakpoint sequences, and preimplantation genetic haplotyping (PGH) was then used to discard embryos with cryptic translocations. RESULTS: Cryptic translocations were found in all four families, and familial transmission was successfully blocked in one family. CONCLUSION: Whole-genome, low-coverage mate-pair sequencing combined with preimplantation genetic haplotyping methods powerfully and practically identify cryptic translocations and block familial transmissions.

First report on identification and genomic analysis of a novel porcine circovirus (porcine circovirus 4) in cats.

Porcine circovirus type 4 (PCV4) is an emerging circovirus, which has been detected in domestic pigs across various provinces in China and Korea. In this study, we aimed to investigate whether cats are susceptible to PCV4. For this purpose, we collected 116 cat samples from animal hospitals in Sichuan Province, China, between 2021 and 2022. Using a SYBR Green-based real-time PCR assay, we detected PCV4 in 5 out of the 116 clinical samples, indicating a positive rate of 4.31% (5/116) and confirming the presence of PCV4 in cats from Sichuan Province, China. Moreover, we successfully sequenced and analyzed the complete genome of one PCV4 strain (SCGA-Cat) along with 60 reference sequences deposited in the GenBank database. SCGA-Cat exhibited high nucleotide homology (98.2-99.0%) with PCV4 strains from other species, including dogs, pigs, dairy cows, and fur animals. Notably, the SCGA-Cat strain from cats clustered closely with a PCV4 strain derived from a pig collected in Fujian Province, China. To the best of our knowledge, this study represents the first report on the molecular detection of PCV4 in cats worldwide, which prompted us to understand the genetic diversity and cross-species transmission of the ongoing PCV4 cases. However, further investigations are needed to explore the association between PCV4 infection and clinical syndromes in cats.

Photoacoustic spectroscopy-based ppb-level multi-gas sensor using symmetric multi-resonant cavity photoacoustic cell.

In this paper, we propose and experimentally demonstrate a symmetric multi-resonant cavity photoacoustic cell (MR-PAC) with dual microphones detection, based on multi-resonator photoacoustic spectroscopy (MR-PAS). The designed photoacoustic cell contains three interconnected acoustic resonators to facilitate simultaneous control of three lasers for multi-gas sensing. Two microphones are symmetrically located at both sides of photoacoustic cell to implement two-point detection. The length of acoustic resonator is about 50 mm to minimize the photoacoustic cell, and the resonant frequency is around 3000 Hz. Feasibility and performance of the MR-PAC was demonstrated by simultaneous detection of C2H2, NO and CF4 using a near infrared diode laser and two mid infrared quantum cascade lasers. The minimum detection limits (MDLs) of C2H2, NO and CF4 are 480 ppb, 260 ppb and 0.57 ppb respectively with a 1 s integration time at normal atmospheric pressure. This minimized MR-PAS system is promising for the portable multi-gas sensing.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Prokaryotic expression of porcine deltacoronavirus S gene truncated segment and establishment of indirect ELISA detection method.

Porcine deltacoronavirus (PDCoV) is an emerging discovered coronavirus that causes significant losses in the global swine industry. This study aimed to establish an indirect ELISA method for detecting PDCoV antibodies using the truncated gene of PDCoV spike protein (S). The purified S protein was used as the coating antigen for the polyclonal antibody. The conditions were optimized to establish an indirect ELISA detection method for PDCoV based on the S protein, which showed good specificity and no cross-reaction with SVV-VP1, ASFV-P72, GETV-E2, PRV-gE, etc. The method has high repeatability, with coefficients of variation within and between batches less than 10%. Compared with the commercial kit, the positive coincidence rate is 86.40%, the negative coincidence rate is 89.43%, and the total coincidence rate is 91.76%. This ELISA can be used for PDCoV serological investigation and antibody evaluation. It can also lay the foundation for further research and development of PDCoV S protein ELISA antibody detection kit.

Laser Linewidth Analysis and Filtering/Fitting Algorithms for Improved TDLAS-Based Optical Gas Sensor.

Tunable Diode Laser Absorption Spectroscopy (TDLAS) has been widely applied in in situ and real-time monitoring of trace gas concentrations. In this paper, an advanced TDLAS-based optical gas sensing system with laser linewidth analysis and filtering/fitting algorithms is proposed and experimentally demonstrated. The linewidth of the laser pulse spectrum is innovatively considered and analyzed in the harmonic detection of the TDLAS model. The adaptive Variational Mode Decomposition-Savitzky Golay (VMD-SG) filtering algorithm is developed to process the raw data and could significantly eliminate the background noise variance by about 31% and signal jitters by about 12.5%. Furthermore, the Radial Basis Function (RBF) neural network is also incorporated and applied to improve the fitting accuracy of the gas sensor. Compared with traditional linear fitting or least squares method (LSM), the RBF neural network brings along the enhanced fitting accuracy within a large dynamic range, achieving an absolute error of below 50 ppmv (about 0.6%) for the maximum 8000 ppmv methane. The proposed technique in this paper is universal and compatible with TDLAS-based gas sensors without hardware modification, allowing direct improvement and optimization for current optical gas sensors.

Contribution of gut microbiota to drug-induced liver injury.

Drug-induced liver injury (DILI) is caused by various drugs with complex pathogenesis, and diverse clinical and pathological phenotypes. Drugs damage the liver directly through drug hepatotoxicity, or indirectly through drug-mediated oxidative stress, immune injury and inflammatory insult, which eventually lead to hepatocyte necrosis. Recent studies have found that the composition, relative content and distribution of gut microbiota in patients and animal models of DILI have changed significantly. It has been confirmed that gut microbial dysbiosis brings about intestinal barrier destruction and microorganisms translocation, and the alteration of microbial metabolites may cause or aggravate DILI. In addition, antibiotics, probiotics, and fecal microbiota transplantation are all emerging as prospective therapeutic methods for DILI by regulating the gut microbiota. In this review, we discussed how the altered gut microbiota participates in DILI.

Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation.

Background & Aims: Hepatocyte transplantation has emerged as a possible treatment option for end-stage liver disease. However, an important obstacle to therapeutic success is the low level of engraftment and proliferation of transplanted hepatocytes, which do not survive long enough to exert therapeutic effects. Thus, we aimed to explore the mechanisms of hepatocyte proliferation in vivo and find a way to promote the growth of transplanted hepatocytes. Methods: Hepatocyte transplantation was performed in Fah -/- mice to explore the mechanisms of hepatocyte proliferation in vivo. Guided by in vivo regeneration mechanisms, we identified compounds that promote hepatocyte proliferation in vitro. The in vivo effects of these compounds on transplanted hepatocytes were then evaluated. Results: The transplanted mature hepatocytes were found to dedifferentiate into hepatic progenitor cells (HPCs), which proliferate and then convert back to a mature state at the completion of liver repopulation. The combination of two small molecules Y-27632 (Y, ROCK inhibitor) and CHIR99021 (C, Wnt agonist) could convert mouse primary hepatocytes into HPCs, which could be passaged for more than 30 passages in vitro. Moreover, YC could stimulate the proliferation of transplanted hepatocytes in Fah -/- livers by promoting their conversion into HPCs. Netarsudil (N) and LY2090314 (L), two clinically used drugs which target the same pathways as YC, could also promote hepatocyte proliferation in vitro and in vivo, by facilitating HPC conversion. Conclusions: Our work suggests drugs promoting hepatocyte dedifferentiation may facilitate the growth of transplanted hepatocytes in vivo and may facilitate the application of hepatocyte therapy. Impact and implications: Hepatocyte transplantation may be a treatment option for patients with end-stage liver disease. However, one important obstacle to hepatocyte therapy is the low level of engraftment and proliferation of the transplanted hepatocytes. Herein, we show that small molecule compounds which promote hepatocyte proliferation in vitro by facilitating dedifferentiation, could promote the growth of transplanted hepatocytes in vivo and may facilitate the application of hepatocyte therapy.

The first dog-origin porcine circovirus type 4 complete genomic sequence have high homology with that of pig-derived strains.

Introduction: Porcine circovirus 4 (PCV4) was discovered in 2019 and then proved to be pathogenic to piglets. Nevertheless, few studies were currently available about PCV4 infection in species other than pigs and there is no information about the prevalence of PCV4 in dogs. Methods: To fill this gap, 264 dog samples were collected from animal hospitals in the Southwest of China from 2021 to 2022 and screened for PCV4. Moreover, the complete genome of one PCV4 strain (SCABTC-Dog2022) were obtained successfully and shared a high identity (97.9-99.0%) with other PCV4 strains derived from pigs, dairy cows, raccoon dogs and foxes. The SCABTC-Dog2022 were analyzed together with 51 reference sequences. Results and Discussion: The detected results showed a low percentage of PCV-4 DNA (1.14%, 3/264), indicating that PCV4 could be identified in dogs in southwest China. Phylogenetic tree showed that SCABTC-Dog2022 strain derived from dog were clustered in a closed relative and geographically coherent branch with other PCV4 strains collected from four provinces (Sichuan, Fujian, Hunan and Inner Mongolia) of China. To our knowledge, it is the first detection of PCV4 in dogs globally. The association between PCV4 status and clinical syndromes in dogs deserves additional investigations.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

[Reflections on supervision strategies of new Tibetan drug registration].

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.

[Minimal clinically important difference of the frequency of bowel movement for patients with chronic severe functional constipation treated with acupuncture].

OBJECTIVE: To estimate the minimal clinically important difference (MCID) of the frequency of bowel movement for the patients with chronic severe functional constipation treated with acupuncture so as to provide the evidence for the clinical decision. METHODS: In this study, 813 patients with chronic severe functional constipation treated with acupuncture in two previous randomized controlled trials were included. Through the anchor-based method (anchored by the item 28 "satisfaction with previous treatment" of the patient assessment of constipation-quality of life [PAC-QOL]) and the distribution-based method, the MCID of the weekly frequency of complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) was analyzed statistically in the patients. RESULTS: The MCID of the mean weekly frequency of CSBM and SBM was 1.3 times and 1.6 times in patients with chronic severe functional constipation treated with acupuncture, respectively. CONCLUSION: The mean increase of the weekly CSMB is ≥ 1.3 times and that of SBM is ≥ 1.6 times after treatment when compared with the baseline respectively, suggesting the clinical significance.

First molecular detection and genetic analysis of porcine circovirus 4 in the Southwest of China during 2021-2022.

Porcine circovirus 4 (PCV4) was identified in 2019 as a novel circovirus species and then proved to be pathogenic to piglets. However, there is a lack of its prevalence in the Southwest of China. To investigate whether PCV4 DNA existed in the Southwest of China, 374 samples were collected from diseased pigs during 2021-2022 and detected by a real-time PCR assay. The results showed that the positive rate of PCV4 was 1.34% (5/374) at sample level, and PCV4 was detected in two of 12 cities, demonstrating that PCV4 could be detected in pig farms in the Southwest of China, but its prevalence was low. Furthermore, one PCV4 strain (SC-GA2022ABTC) was sequenced in this study and shared a high identity (98.1-99.7%) with reference strains at the genome level. Combining genetic evolution analysis with amino acid sequence analysis, three genotypes PCV4a, PCV4b, and PCV4c were temporarily identified, and the SC-GA2022ABTC strain belonged to PCV4c with a specific amino acid pattern (239V for Rep protein, 27N, 28R, and 212M for Cap protein). Phylogenetic tree and amino acid alignment showed that PCV4 had an ancient ancestor with mink circovirus. In conclusion, the present study was the first to report the discovery and the evolutionary analysis of the PCV4 genome in pig herds of the Southwest of China and provide insight into the molecular epidemiology of PCV4.

IL6 supports long-term expansion of hepatocytes in vitro.

Hepatocytes are very difficult to expand in vitro. A few studies have demonstrated that chemical cocktails with growth factors or Wnt ligands can support long-term expansion of hepatocytes via dedifferentiation. However, the culture conditions are complex, and clonal expansion of hepatic progenitors with full differentiation capacity are rarely reported. Here, we discover IL6, combined with EGF and HGF, promotes long-term expansion (>30 passages in ~150 days with theoretical expansion of ~1035 times) of primary mouse hepatocytes in vitro in simple 2D culture, by converting hepatocytes into induced hepatic progenitor cells (iHPCs), which maintain the capacity of differentiation into hepatocytes. IL6 also supports the establishment of single hepatocyte-derived iHPC clones. The summation of the downstream STAT3, ERK and AKT pathways induces a number of transcription factors which support rapid growth. This physiological and simple way may provide ideas for culturing previously difficult-to-culture cell types and support their future applications.

Remodeling nanodroplets into hierarchical mesoporous silica nanoreactors with multiple chambers.

Multi-chambered architectures have attracted much attention due to the ability to establish multifunctional partitions in different chambers, but manipulating the chamber numbers and coupling multi-functionality within the multi-chambered mesoporous nanoparticle remains a challenge. Herein, we propose a nanodroplet remodeling strategy for the synthesis of hierarchical multi-chambered mesoporous silica nanoparticles with tunable architectures. Typically, the dual-chambered nanoparticles with a high surface area of ~469 m2 g-1 present two interconnected cavities like a calabash. Furthermore, based on this nanodroplet remodeling strategy, multiple species (magnetic, catalytic, optic, etc.) can be separately anchored in different chamber without obvious mutual-crosstalk. We design a dual-chambered mesoporous nanoreactors with spatial isolation of Au and Pd active-sites for the cascade synthesis of 2-phenylindole from 1-nitro-2-(phenylethynyl)benzene. Due to the efficient mass transfer of reactants and intermediates in the dual-chambered structure, the selectivity of the target product reaches to ~76.5%, far exceeding that of single-chambered nanoreactors (~41.3%).