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Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivo show that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. In summary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming, providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a new idea to design percutaneous implantation materials.

Abstract To investigate the effects of high temperature and carbon fiber-bar reinforcement on the dynamic mechanical properties of concrete materials, a muffle furnace was used to treat two kinds of specimens, plain and carbon fiber-bar reinforced concrete, at high temperatures of 25, 200, 400 and 600 °C. Impact compression tests were carried out on two specimens after high-temperature exposure using a Hopkinson pressure bar (SHPB) test setup combined with a high-speed camera device to observe the crack extension process of the specimens. The effects of high temperature and carbon fiber-bar reinforcement on the peak stress, energy dissipation density, crack propagation and fractal dimension of the concrete were analyzed. The results showed that the corresponding peak strengths of the plain concrete specimens at 25, 200, 400, and 600 °C were 88.37, 93.21, 68.85, and 54.90 MPa, respectively, and the peak strengths after the high-temperature exposure first increased slightly and then decreased rapidly. The mean peak strengths corresponding to the carbon fiber-bar reinforced concrete specimens after high-temperature action at 25, 200, 400, and 600 °C are 1.13, 1.13, 1.21, and 1.19 times that of plain concrete, respectively, and the mean crushing energy consumption densities are 1.27, 1.31, 1.73, and 1.59 times that of plain concrete, respectively. The addition of carbon fiber-bar reinforcement significantly enhanced the impact resistance and energy dissipation of the concrete structure, and the higher the temperature was, the more significant the increase. An increase in temperature increases the number of crack extensions and width, and the high tensile strength of the carbon fiber-bar reinforcement and the synergistic effect with the concrete material reduce the degree of crack extension in the specimen. The fractal dimension of the concrete ranged from 1.92 to 2.68, that of the carbon fiber-bar reinforced concrete specimens ranged from 1.61 to 2.42, and the mean values of the corresponding fractal dimensions of the plain concrete specimens after high-temperature effects at 25, 200, 400, and 600 °C were 1.19, 1.21, 1.10, and 1.11 times those of the fiber-reinforced concrete specimens, respectively. The incorporation of carbon fiber-bar reinforcement reduces the degree of rupture and fragmentation of concrete under impact loading and improves the safety and stability of concrete structures.

Abstract In order to investigate the effects of strain rate and water saturation on the energy dissipation and crack growth of tuff, uniaxial compression tests were carried out on dry and water saturated tuff with different strain rates using an electro-hydraulic servo press and a 50 mm diameter split Hopkinson pressure rod (SHPB) device. High-speed camera and Image J image analysis software were used to obtain the crack growth process of the specimen under impact load, and fractal dimension was introduced to quantitatively study the crack growth degree. The results show that more than 90% of the energy is stored in the specimen as elastic energy when it reaches the peak stress under static load. The average total energy of water-saturated specimens is 67.55% of that of dry specimens. The average energy dissipation density of water-saturated specimens under 0.3 MPa, 0.4 MPa and 0.5 MPa air pressure is 0.79, 0.91 and 0.92 times of that of dry specimens, respectively. Water-saturated specimens will deteriorate and thus reduce their energy storage and energy absorption effects. The reflected energy, transmitted energy, absorbed energy and incident energy are linear, logarithmic and linear functions, respectively, and the energy absorptivity and specific energy absorptivity of water-saturated specimens are lower than those of dry specimens. Due to the existence of “stefan” effect, the increase of energy dissipation density of water-saturated specimen at high strain rate is greater than that of dry specimen. The mean fractal dimension of water-saturated specimens under 0.3 MPa, 0.4 MPa and 0.5 MPa is 1.09, 1.05 and 1.16 times that of dry specimens. At the same strain rate, the number and width of cracks in water-saturated specimens are larger than that in dry specimens. Water-saturated behavior reduces the energy absorption capacity of tuff, increases the fractal dimension of crack growth, and significantly reduces the resistance of water-saturated rock to external loads.

Abstract Regulatory T cells (Tregs) are essential to the negative regulation of the immune system, as they avoid excessive inflammation and mediate tumor development. The abundance of Tregs in tumor tissues suggests that Tregs may be eliminated or functionally inhibited to stimulate antitumor immunity. However, immunotherapy targeting Tregs has been severely hampered by autoimmune diseases due to the systemic elimination of Tregs. Recently, emerging studies have shown that metabolic regulation can specifically target tumor-infiltrating immune cells, and lipid accumulation in TME is associated with immunosuppression. Nevertheless, how Tregs actively regulate metabolic reprogramming to outcompete effector T cells (Teffs), and how lipid metabolic reprogramming contributes to the immunomodulatory capacity of Tregs have not been fully discussed. This review will discuss the physiological processes by which lipid accumulation confers a metabolic advantage to tumor-infiltrating Tregs (TI-Tregs) and amplifies their immunosuppressive functions. Furthermore, we will provide a summary of the driving effects of various metabolic regulators on the metabolic reprogramming of Tregs. Finally, we propose that targeting the lipid metabolism of TI-Tregs could be efficacious either alone or in conjunction with immune checkpoint therapy.

Sex control techniques are in great demand for aquaculture because of the huge benefits of mono-sex production. In a previous study on yellow catfish (Tachysurus fulvidraco), intersex individuals were produced by administrating 17α-methyltestosterone (MT) or aromatase inhibitor letrozole (LZ). The ovarian and testicular portions of intersexual gonads developed well and were completely separated, arousing our interest in producing self-fertilizable fish and clone-like fish populations. In this study, yellow catfish fry were treated with a combination of MT and LZ at a low dose (5 mg kg−1 MT, 300 mg kg−1 LZ) at a low water temperature (27.0 °C, mixed sex-producing temperature, LL group) and a high temperature (33.5 °C, male-producing temperature, HL group), and with a high dose (10 mg kg−1 MT, 600 mg kg−1 LZ) at a low water temperature (LH group), during 12–65 days post-hatching, the critical period of sex differentiation. Both XX and XY intersex were produced with different percentages at the same time through co-treatment with MT and LZ, with or without the help of male-producing temperature. The highest percentage of XY intersex (53% in XY, 36% in XX and XY) and XX intersex (47% in XX, 25% in XX and XY) was produced in LH and HL groups, respectively. Results of gonadal morphology, histology, and sperm dynamic analysis indicate that some XX and XY intersex individuals were capable of self-fertilization through artificial insemination. The reproductive performance of these intersex individuals was then investigated by injecting spawning agents, dissecting gonads, and artificially fertilizing eggs with their own sperm. The XX, XY, and YY genotypic individuals were produced by the self-fertilization of XY intersex individuals. The present study successfully produced high percentages of XX and XY intersex and conducted self-fertilization by mating the eggs and sperm of a single intersex individual. Self-fertilization in fish will show great potential in aquaculture genetics and breeding, for example, generating highly homozygous (or ‘‘clonal’’) genetic material, producing mono-sex populations, and identifying unknown sex determination modes. In particular, the cloning method of producing genetic materials will be greatly beneficial for maintaining advantageous traits through self-fertilization generation after generation.

Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the “sweating” primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.

Abstract Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.

Abstract Background The influencing factors, especially time to treatment (TTT), for T1b/T2 gallbladder cancer (GBC) patients remain unknown. We aimed to identify the influencing factors on survival and surgical approaches selection for T1b/T2 GBC. Methods We retrospectively screened GBC patients between January 2011 and August 2018 from our hospital. Clinical variables, including patient characteristics, TTT, overall survival (OS), disease‐free survival (DFS), surgery‐related outcomes, and surgical approaches were collected. Results A total of 114 T1b/T2 GBC patients who underwent radical resection were included. Based on the median TTT of 7.5 days, the study cohort was divided into short TTT group (TTT ≤7 days, n = 57) and long TTT group (TTT >7 days, n = 57). Referrals were identified as the primary factor prolonging TTT (p 0.05) between both groups. Decreased referrals (p = 0.005), fewer positive lymph nodes (LNs; p = 0.004), and well tumor differentiation (p = 0.004) were all associated with better OS, while fewer positive LNs (p = 0.049) were associated with better DFS. Subgroup analyses revealed no significant difference in survival between patients undergoing laparoscopic or open approach in different TTT groups (all p > 0.05). And secondary subgroup analyses found no significance in survival and surgery‐related outcomes between different TTT groups of incidental GBC patients (all p > 0.05). Conclusions Positive LNs and tumor differentiation were prognostic factors for T1b/T2 GBC survival. Referrals associating with poor OS would delay TTT, while the prolonged TTT would not impact survival, surgery‐related outcomes, and surgical approaches decisions in T1b/T2 GBC patients.

Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity, from preventive and diagnostic to therapeutic fields. Lipoproteins, because of their inherent blood-brain barrier permeability and lesion-homing capability, have been identified as promising strategies for high-performance theranostics of brain diseases. However, the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes, which can be critical for individual therapeutics and clinical translation. To address these issues, lipoprotein-inspired nano drug-delivery systems (nano-DDSs), which have been learned from nature, have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions. In this review, the barriers in brain disease treatment, advantages of state-of-the-art lipoprotein-inspired nano-DDSs, and bio-interactions of such nano-DDSs are highlighted. Furthermore, the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized. Specifically, the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed. Finally, the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles, such as exosomes, cell membranes, and bacteria, are discussed.

In order to achieve the ambitious goal of “carbon neutrality”, countries around the world are striving to develop clean energy. Against this background, this paper takes China and Italy as representatives of developing and developed countries to summarize the energy structure composition and development overview of the two countries. The paper analyzes the serious challenges facing the future energy development of both countries and investigates the possibilities of energy cooperation between the two countries, taking into account their respective advantages in energy development. By comparing the policies issued by the two governments to encourage clean energy development, this paper analyzes the severe challenges faced by the two countries’ energy development in the future and combines their respective energy development advantages to look forward to the possibility of energy cooperation between the two countries in the future. This lays the foundation for China and Italy to build an “Energy Road” after the “Silk Road”.

Abstract Background Penfluridol (PF) is an FDA-approved antipsychotic drug that has recently been shown to have anticancer activity. However, the anticancer effects and underlying mechanisms of PF are not well-established in gallbladder cancer (GBC). Methods The anticancer efficacy of PF on GBC was investigated via a series of cell functions experiments, including cell viability, colony formation, apoptosis assays, and so on. The corresponding signaling changes after PF treatment were explored by western blotting. Then, nude mice were utilized to study and test the anticancer activity of PF in vivo. Besides, glucose consumption and lactic production assays were used to detect the glycolysis alteration. Results In this study, we discovered that PF greatly inhibited the proliferation and invasion ability of GBC cells (GBCs). The glucose consumption and lactic generation ability of GBCs were dramatically elevated following PF treatment. Additionally, we discovered that inhibiting glycolysis could improve PF's anticancer efficacy. Further studies established that the activation of the AMPK/PFKFB3 signaling pathway medicated glycolysis after PF treatment. We proved mechanistically that inhibition of AMPK/PFKFB3 singling pathway mediated glycolysis was a potential synergetic strategy to improve the anticancer efficacy of PF on GBC. Conclusions By inhibiting AMPK, the anticancer effects of PF on GBCs were amplified. As a result, our investigations shed new light on the possibility of repurposing PF as an anticancer drug for GBC, and AMPK inhibition in combination with PF may represent a novel therapeutic strategy for GBC. Graphical abstract Video abstract

Abstract Background Recent studies exploring the roles of invasion-metastasis associated miRNAs in gallbladder cancer (GBC) are limited. In the study, we aimed to identify the invasion-metastasis associated miRNAs in GBC by bioinformatics and experimental validation. Methods MiRNAs of different expression were identified by comparing GBC tumor samples with different survival from Gene Expression Omnibus database. MiRTarBase was used for identifying the potential target genes of miRNAs. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. And miRNA-gene and protein–protein interaction (PPI) network were constructed for hub genes evaluation. We further explored and compared miR-642a-3p and miR-145-5p expression in both The Cancer Genome Atlas database and our hospital data. Finally, quantitative real-time PCR, wound healing assay, and Transwell assay were conducted to validate the invasion-metastasis associated miRNAs in GBC. Results In GSE104165 database, 25 up-regulated and 97 down-regulated miRNAs were detected with significantly different expression in GBC tumor samples. Then, 477 potential target genes were identified from the 2 most up-regulated miRNAs (miR-4430 and miR-642a-3p) and 268 genes from the 2 most down-regulated miRNAs (miR-451a and miR-145-5p). After GO and KEGG analysis, mTOR and PI3K-Akt signaling pathways were found associated with the potential target genes. Based on PPI network, the top 10 highest degree hub nodes were selected for hub genes. Furthermore, the miRNA-hub gene network showed significant miR-642a-3p up-regulation and miR-145-5p down-regulation in both GBC tissues and cell lines. In the experimental validation, miR-145-5p up-regulation and miR-642a-3p down-regulation were confirmed to suppress GBC invasion and metastasis. Conclusions MiR-642a-3p and miR-145-5p were identified as invasion-metastasis associated miRNAs via bioinformatics and experimental validation, and both up-regulation of miR-642a-3p and down-regulation of miR-145-5p would be served as novel treatment options for GBC in the future.

Abstract DNA molecules are subject to various lesions that can be detrimental to the cells. DNA damage response (DDR) pathways encompass a variety of mechanisms that cells employ in response to DNA damage. While DDR promotes genomic stability in normal cells, it also protects cancer cells from DNA lesions, particularly against exogenous DNA‐damaging agents. Therefore, DDR pathways can be exploited to account for resistance to chemotherapy and radiotherapy and have the potential to be targeted in cancer treatment. Apart from the poly (ADP‐ribose) polymerase (PARP) inhibitors used in BRCA‐mutant cancers, other DDR inhibitors are being developed and tested in clinical trials. Based on the synthetic lethality theory, combination therapies utilizing DDR inhibitors have been explored and are currently undergoing clinical trials, with promising results in cancer treatment. Combination therapies typically employ a DDR inhibitor to sensitize cancer cells to traditional chemotherapeutic agents, radiotherapy, immunotherapy, and even PARP inhibitors. Herein, we focus on recent advances in DDR inhibitor‐based combination therapies other than PARP inhibitors, explore the advantages and disadvantages of the strategies, and discuss the current challenges and future perspectives.

PurposeTo explore the effect of corneal spherical aberration on the visual acuity and visual quality of eyes implanted with the TECNIS Symfony intraocular lens (IOL).MethodsA total of 43 patients with age-related cataract (60 eyes) undergoing phacoemulsification and TECNIS Symfony IOL implantation were enrolled in this study. The uncorrected distance (UDVA), intermediate (UIVA), near visual acuity (UNVA), corrected distance visual acuity (CDVA), contrast sensitivity, and ocular spherical aberration were recorded 3 months after surgery. Preoperative and postoperative corneal spherical aberration were also measured using the iTrace device. Objective scattering index (OSI), modulation transfer function cut-off frequency (MTF cut-off), and Strehl ratio (SR) were measured by the Optical Quality Analyzing System. Catquest-9SF questionnaire were applied too. Spearman’s correlation analysis was used to evaluate the relationship between spherical aberration and visual quality parameters.ResultsPatients were satisfied with their postoperatively visual quality. And the postoperative logMAR UDVA, UIVA, UNVA, and CDVA was 0.05 ± 0.07, 0.04 ± 0.06, 0.15 ± 0.07, and 0.03 ± 0.05, respectively. The mean preoperative corneal spherical aberration was 0.24 ± 0.10 μm, which is the only factor influencing postoperatively UNVA, and it was negatively correlated with UNVA and glare contrast sensitivity under 18 cpd (cycle/degree, cpd) spatial frequency (r = −0.403, −0.300, −0.360; all P < 0.05). Additionally, the greater the residual spherical aberration of the cornea, the better the near vision after operation. The mean postoperative ocular spherical aberration was −0.03 ± 0.07 μm, it was not correlated with visual acuity, contrast sensitivity, and visual quality (all P > 0.05).ConclusionPreoperative positive spherical aberration can benefit near vision while decrease contrast sensitivities at high spatial frequencies when implanted with the TECNIS Symfony IOL.

It is an urgent need to tackle drug-resistance microbial infections that are associated with implantable biomedical devices. Host defense peptide-mimicking polymers have been actively explored in recent years to fight against drug-resistant microbes. Our recent report on lithium hexamethyldisilazide-initiated superfast polymerization on amino acid N-carboxyanhydrides enables the quick synthesis of host defense peptide-mimicking peptide polymers. Here we reported a facile and cost-effective thermoplastic polyurethane (TPU) surface modification of peptide polymer (DLL: BLG = 90 : 10) using plasma surface activation and substitution reaction between thiol and bromide groups. The peptide polymer-modified TPU surfaces exhibited board-spectrum antibacterial property as well as effective contact-killing ability in vitro. Furthermore, the peptide polymer-modified TPU surfaces showed excellent biocompatibility, displaying no hemolysis and cytotoxicity. In vivo study using methicillin-resistant Staphylococcus aureus (MRSA) for subcutaneous implantation infectious model showed that peptide polymer-modified TPU surfaces revealed obvious suppression of infection and great histocompatibility, compared to bare TPU surfaces. We further explored the antimicrobial mechanism of the peptide polymer-modified TPU surfaces, which revealed a surface contact-killing mechanism by disrupting the bacterial membrane. These results demonstrated great potential of the peptide-modified TPU surfaces for practical application to combat bacterial infections that are associated with implantable materials and devices.

An innovative optical frequency-domain reflectometry (OFDR)-based distributed temperature sensing method is proposed that utilizes a Rayleigh backscattering enhanced fiber (RBEF) as the sensing medium. The RBEF features randomly high backscattering points; the analysis of the fiber position shift of these points before and after the temperature change along the fiber is achieved using the sliding cross-correlation method. The fiber position and temperature variation can be accurately demodulated by calibrating the mathematical relationship between the high backscattering point position along the RBEF and the temperature variation. Experimental results reveal a linear relationship between temperature variation and the total position displacement of high backscattering points. The temperature sensing sensitivity coefficient is 7.814 μm/(m·°C), with an average relative error temperature measurement of −1.12% and positioning error as low as 0.02 m for the temperature-influenced fiber segment. In the proposed demodulation method, the spatial resolution of temperature sensing is determined by the distribution of high backscattering points. The temperature sensing resolution depends on the spatial resolution of the OFDR system and the length of the temperature-influenced fiber. With an OFDR system spatial resolution of 12.5 μm, the temperature sensing resolution reaches 0.418 °C per meter of RBEF under test.

Abstract Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available. Microbial metabolites have been a rich source of antimicrobial agents and have inspired the authors to design and obtain potent and selective antifungal agents, poly(DL‐diaminopropionic acid) (PDAP) from the ring‐opening polymerization of β‐amino acid N‐thiocarboxyanhydrides, by mimicking ε‐poly‐lysine. PDAP kills fungal cells by penetrating the fungal cytoplasm, generating reactive oxygen, and inducing fungal apoptosis. The optimal PDAP displays potent antifungal activity with minimum inhibitory concentration as low as 0.4 µg mL−1 against Candida albicans, negligible hemolysis and cytotoxicity, and no susceptibility to antifungal resistance. In addition, PDAP effectively inhibits the formation of fungal biofilms and eradicates the mature biofilms. In vivo studies show that PDAP is safe and effective in treating fungal keratitis, which suggests PDAPs as promising new antifungal agents.

Abstract Gallbladder cancer (GBC) is a rare but the most malignant type of biliary tract tumor. It is usually diagnosed at an advanced stage and conventional treatments are unsatisfactory. As a proteasome inhibitor, bortezomib (BTZ) exhibits excellent antitumor ability in GBC. However, the long‐term treatment efficacy is limited by its resistance, poor stability, and high toxicity. Herein, BTZ‐encapsulated pH‐responsive copolymeric nanoparticles with estrone (ES‐NP(BTZ; Ce6)) for GBC‐specific targeted therapy is reported. Due to the high estrogen receptor expression in GBC, ES‐NP(BTZ; Ce6) can rapidly enter the cells and accumulate near the nucleus via ES‐mediated endocytosis. Under acidic tumor microenvironment (TME) and 808 nm laser irradiation, BTZ is released and ROS is generated by Ce6 to destroy the “bounce‐back” response pathway proteins, such as DDI2 and p97, which can effectively inhibit proteasomes and increase apoptosis. Compared to the traditional treatment using BTZ monotherapy, ES‐NP(BTZ; Ce6) can significantly impede disease progression at lower BTZ concentrations and improve its resistance. Moreover, ES‐NP(BTZ; Ce6) demonstrates similar antitumor abilities in patient‐derived xenograft animal models and five other types of solid tumor cells, revealing its potential as a broad‐spectrum antitumor formulation.

BackgroundEnhanced recovery care could alleviate surgical stress and accelerate the recovery rates of patients. Previous studies showed the benefits of enhanced recovery after surgery program in liver surgery, but the exact role in laparoscopic hepatectomy is still unclear.AimWe aimed to perform a meta-analysis to evaluate the safety and efficacy of enhanced recovery after a surgery program in laparoscopic hepatectomy.MethodsThe relative studies from a specific search of PUBMED, EMBASE, OVID, and Cochrane database from June 2008 to February 2022 were selected and included in this meta-analysis. The primary outcomes included length of hospital stay, duration to functional recovery, and overall postoperative complication rate. The secondary outcomes included operative time, intraoperative blood loss, cost of hospitalization, readmission rate, Grade I complication rate, and Grade II–V complication rate.ResultsA total of six studies with 643 patients [enhanced recovery care (n = 274) vs. traditional care (n = 369)] were eligible for analysis. These comprised three randomized controlled trials and three retrospective studies. Enhanced recovery care group was associated with decreased hospital stay [standard mean difference (SMD) = −0.56, 95% confidence interval (CI) = −0.83~−0.28, p < 0.0001], shorter duration to functional recovery (SMD = −1.14, 95% CI = −1.92~−0.37, p = 0.004), and lower cost of hospitalization Mean Difference (MD) = −1,539.62, 95% CI = −1992.85~−1086.39, p < 0.00001). Moreover, a lower overall postoperative complication rate was observed in enhanced recovery care group [Risk ratio (RR) = 0.64, 95% CI = 0.51~0.80, p < 0.0001] as well as lower Grade II–V complication rate (RR = 0.55, 95% CI = 0.38~0.80, p = 0.002), while there was no significant difference in intraoperative blood loss (MD = −65.75, 95% CI = −158.47~26.97, p = 0.16), operative time (MD = −5.44, 95% CI = −43.46~32.58, p = 0.78), intraoperative blood transfusion rate [Odds ratio (OR) = 0.71, 95% CI = 0.41~1.22, p = 0.22], and Grade I complication rate (RR = 0.73, 95% CI = 0.53~1.03, p = 0.07).ConclusionEnhanced recovery care in laparoscopic hepatectomy should be recommended, because it is not only safe and effective, but also can accelerate the postoperative recovery and lighten the financial burden of patients.

ObjectivesThe primary laparoscopic approach (PLA) for T1b/T2 gallbladder cancer (GBC) remains contradicted. We aimed to compare the perioperative and long-term outcomes after PLA versus open approach (OA) for T1b/T2 GBC.MethodsPatients with resected T1b/T2 GBC were selected from our hospital between January 2011 and August 2018. Overall survival (OS), disease-free survival (DFS), and several secondary outcomes were used to evaluate safety and effectiveness. Subgroup analyses were performed to identify significant risk factors for OS/DFS in GBC patients undergoing PLA/OA.ResultsA total of 114 patients who underwent OA (n = 61) or PLA (n = 53) were included in the study. The percent of PLA cases was increased over time from 40.0% in 2011 to 70.0% in 2018 (p < 0.05). There was no significant difference in OS [hazard ratio (HR), 1.572; 95% confidence interval (CI), 0.866–2.855; p = 0.13] and DFS (HR, 1.225; 95% CI, 0.677–2.218; p = 0.49). No significance was found for intraoperative drainage placement (p = 0.253), intraoperative blood loss (p = 0.497), operation time (p = 0.105), postoperative hospitalization (p = 0.797), positive LNs (p = 0.494), total harvested LNs (p = 0.067), and recurrence rates (P = 0.334). Subgroup analyses demonstrated no significance of conversion rates after PLA (all p > 0.05). Patients undergoing PLA with good/poor OS would have similar recurrence rates (p = 0.402). Positive LNs (p = 0.032) and tumor differentiation (p = 0.048) were identified as risk factors for OS after PLA, while positive LNs (p = 0.005) was identified for OS after OA. Moreover, age (p = 0.013), gallbladder stone (p = 0.008), tumor size (p = 0.028), and positive LNs (p = 0.044) were potential risk factors for DFS after OA.ConclusionsPLA for T1b/T2 GBC was comparable to OA in terms of perioperative and long-term outcomes. Less positive LNs and well-differentiated tumors were independent predictors for better OS after PLA, and less positive LNs were also identified for better OS after OA. Additionally, younger age, without gallbladder stone, smaller tumor size, and less positive LNs were potential risk factors for better DFS after OA.

Mobile cloud computing (MCC) enables the mobile devices to offload their applications to the cloud and thus greatly enriches the types of applications on mobile devices and enhances the quality of service of the applications. Under various circumstances, researchers have put forward several MCC architectures. However, how to reduce the response latency while efficiently utilizing the idle service capacities of the mobile devices still remains a challenge. In this paper, we firstly give a definition of MCC and divide the recently proposed architectures into four categories. Secondly, we present a Hybrid Local Mobile Cloud Model (HLMCM) by extending the Cloudlet architecture. Then, after formulating the application scheduling problems in HLMCM and bringing forward the Hybrid Ant Colony algorithm based Application Scheduling (HACAS) algorithm, we finally validate the efficiency of the HACAS algorithm by simulation experiments.