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Recently, flexible transparent conductive films composed of metal nanowires have received significant interest, particularly for flexible electronics. However, the high contact resistance among metal nanowires and the weak bonding effect between metal nanowires and substrates often result in films whose conductivity, adhesion, and flexibility fall short of the stringent requirements demanded by real-world uses. We developed a simple method to fabricate high-performance flexible transparent conductive films via successively spin-coating silver nanowires (AgNWs) and acidic silica sol onto the surface of the substrate. Under the capillary force of ethanol and the etching effect of hydrochloric acid, the adjacent AgNWs are induced to chemically weld in situ to form a stable network. The resulting composite film exhibits a sheet resistance of only 8.5 Ω/sq, marking an impressive 80% decrease compared with the pristine AgNW film. Meanwhile, the silica sol acts as a filler, improving light transmittance while further reinforcing the network structure and firmly bonding it to the substrate. Thus, the delamination of the nanowires under bending motion is effectively inhibited, and the resulting film was endowed with resistance remaining below 15 Ω/sq after 3000 bending and 200 tape peeling. The energy-efficient in situ chemical welding and reinforcement method for nanowires provides an innovative strategy for the batch preparation of flexible transparent conductive films.

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout ( Sigmar1 -/- ) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Dietary pollution by polystyrene microplastics (MPs) can cause hepatic injuries and microbial dysbiosis. Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, exerts beneficial effects on the liver by modulating the gut microbiota. However, the role of microbiota in MPs-induced hepatic injuries and the protective effect of EGCG have not been clarified. Here, 5 μm MPs were orally administered to mice to induce hepatic injuries. Subsequently, antibiotic cocktail (ABX) and fecal microbial transplant (FMT) experiments were performed to investigate the underlying microbial mechanisms. Additionally, EGCG was orally administered to mice to explore its protection against MPs-induced hepatic injuries. Our results showed that MPs activated systemic and hepatic inflammation, promoted fibrosis, and altered the liver metabolome; meanwhile, MPs damaged the gut homeostasis by disturbing the gut microbiome, promoting colonic inflammation, and impairing the intestinal barrier. Notably, MPs reduced the abundance of the probiotics Akkermansia, Mucispirillum, and Faecalibaculum while increasing the pathogenic Tuzzerella. Interestingly, the elimination of gut microbiota mitigated MPs-induced colonic inflammation and intestinal barrier impairment. Moreover, ABX ameliorated MPs-induced systemic and hepatic inflammation but not fibrosis. Correspondingly, microbiota from MPs-administered mice induced colonic, systemic, and hepatic inflammation, while their profibrosis effect on the liver was not observed. Finally, EGCG elevated the abundance of probiotics and effectively repressed MPs-induced colonic inflammation. MPs-induced systemic and hepatic inflammation, fibrosis, and remodeling of the liver metabolome were also attenuated by EGCG. These findings illustrated that gut microbiota contributed to MPs-induced colonic and hepatic injuries, while EGCG could serve as a potential prevention strategy for these adverse consequences.

Overcoming the instability and poor recyclability during the practical applications of contaminant scavengers is a challenging topic. Herein, a three-dimensional (3D) interconnected carbon aerogel (nZVI@Fe 2 O 3 /PC) embedding a core-shell nanostructure of nZVI@Fe 2 O 3 was elaborately designed and fabricated via an in-situ self-assembly process. The porous carbon with 3D network architecture exhibits strong adsorption towards various antibiotic contaminants in water, where the stably embedded nZVI@Fe 2 O 3 nanoparticles not only serve as magnetic seeds for recycling, but also avoid the shedding and oxidation of nZVI in the adsorption process. As a result, nZVI@Fe 2 O 3 /PC efficiently captures sulfamethoxazole (SMX), sulfamethazine (SMZ), ciprofloxacin (CIP), tetracycline (TC) and other antibiotics in water. In particular, an excellent adsorptive removal capacity of 329 mg g -1 and a rapid capture kinetics (99% of removal efficiency in 10 min) under a wide pH adaptability (2-8) are achieved using nZVI@Fe 2 O 3 /PC as an SMX scavenger. nZVI@Fe 2 O 3 /PC displays exceptional long-term stability given that it shows excellent magnetic property after it is stored in water solution for 60 d, making it an ideal stable scavenger for contaminants in an etching-resistant and efficient manner. This work would also provide a general strategy to develop other stable iron-based functional architectures for efficient catalytic degradation, energy conversion and biomedicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Assisted reproductive technology has continued to develop in recent years, the technology has become more and more mature, and it has improved the total gestational age of the population. Assisted reproductive technology has improved twin pregnancy rates with the use of ovulation-inducing drugs. The risk factor of twins is much higher than singletons, and adverse pregnancy outcomes such as stillbirth and premature birth are more likely to occur than singletons, especially the special complications of monochorionic twins (MC), and the neonatal mortality and morbidity are also increased. Prenatal diagnosis and prognosis of twin pregnancy, as well as therapeutic interventions, are of current concern. Ultrasound can realize the understanding of intrauterine growth and development of twin pregnancy fetuses during pregnancy, can more accurately determine gestational age, organ function, and maturity, and timely detect fetal growth and development abnormalities in twin pregnancy, while the prognosis and treatment still need further improvement. The purpose of this study was to investigate the clinical value and treatment progress of prenatal ultrasound monitoring in twin pregnancy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Lihua Zou et al.)

In this work, Cu 2 Se/Cu membranes (CSMs) of hierarchical pores were fabricated via chemical dissolution of Cu and Se followed by redeposition of cuprous selenide (Cu 2 Se) on copper membranes (CMs), and applied for adsorption/removal/separation of Hg(II) among a variety of interfering metal ions. The CSM demonstrates the best comprehensive performance among previous Hg(II) adsorption membranes, having high selectivity ( K Hg/M = 2.9 × 10 4 -3.0 × 10 5 ), high efficiency (>99%, 5 s to 3 min), high adsorption capacity (505 mg/g), and high flux (2.0 × 10 6 L m -2 h -1 ). Meanwhile, effects of Hg(II) concentration, flow rate, and the number of membrane layers and adsorption cycles were also investigated on the removal of Hg(II). Moreover, a Cu 2 Se/Cu membrane-plasma (CSM-p) with superhydrophilicity/underwater superoleophobicity was prepared on the basis of CSM, and simultaneous removal of Hg(II) and oil was realized by using CSM and CSM-p in combination. This work not only provides a new reference for design of highly selective, efficient metal ion adsorption/enrichment/separation materials but also presents a novel approach to the removal/enrichment/separation of multiple complex contaminants by the combination of different functional membranes.

In the current work, Cu(I) 1.28 Cu(II) 0.36 Se nanoparticles were synthesized via a simple procedure and were applied for the first time for recognition, adsorption, enrichment, and detection of Hg(II) ions. The experimental results show that 99.9% Hg(II) could be adsorbed by Cu(I) 1.28 Cu(II) 0.36 Se nanoparticles within just 30 s, and the Hg(II) concentration could be lowered down to a super-low level of 0.01 ppb. Cu(I) 1.28 Cu(II) 0.36 Se nanoparticles also demonstrate high selectivity to Hg(II) and Ag(I) among nine representative metal ions. The enrichment experiments show that Hg(II) of ultratrace concentration could be enriched significantly by Cu(I) 1.28 Cu(II) 0.36 Se nanoparticles, and thus, the detection limit of Hg(II) based on inductively coupled plasma emission spectroscopy-mass spectrometry would be pushed down by 2 orders of magnitude. These outstanding features of Cu(I) 1.28 Cu(II) 0.36 Se nanoparticles could be well accounted for in terms of the solubility product principle and the high affinity between selenium and mercury. Cu(I) 1.28 Cu(II) 0.36 Se nanoparticles were also found to have peroxidase-like activity, which could be inhibited by Hg(II) but not by Ag(I). This unique characteristic coupled with the solubility product principle successfully allows recognition and detection of Hg(II) even in the presence of Ag(I), which has a similar p K sp to Hg(II). As a result, the qualitative and quantitative analyses of Hg(II) could be performed by the naked eye and UV-visible spectroscopy, respectively. The current results indicate that Cu(I) 1.28 Cu(II) 0.36 Se nanoparticles not only have great potential in various aspects of dealing with Hg(II) pollution but would also shed light on discovering new nanomaterials to address other heavy metal ions.

We report a portable and highly sensitive Hg 2+ nanosensor, where the CuS nanozyme functions as an Hg 2+ recognition unit, a Hg 2+ enrichment/preconcentration carrier, and a signal amplifier/output unit. The as-designed enrichment-detection integration strategy is customizable and endows the sensor with both a wide detection range from 50 ppt to 400 ppb and a high sensitivity with a minimum detectable Hg 2+ concentration of 50 ppt. In order to make the Hg 2+ nanosensor portable and cost-effective, a commercial RGB sensor is employed here in conjunction with the Hg 2+ -dependent colorimetric reaction. More importantly, the as-developed Hg 2+ nanosensor is feasible for analysis of real samples with satisfactory accuracy (deviation <10%) and reproducibility (recovery ∼82%). Thus, this portable Hg 2+ nanosensor appears to be a viable solution to meet the actual needs of on-site and real-time mercury contamination analysis and may also pave the way to colorimetric nanosensors for other metal ions.

Background: Even with the augmentative application of anal-preservation surgery in low rectal cancer, the role and indications of laparoscopic intersphincteric resection (Lap ISR) are still under debate, especially for T3 or node-positive (T3N0M0, T1-3N+M0) cancer, mainly due to the oncological safety and functional outcomes. INTRABEAM (Carl Zeiss, Germany) intraoperative radiotherapy (IORT) using low-energy X-rays features in accurate irradiation, less exposure, and reduced complications. Taking advantages of Lap ISR and INTRABEAM IORT, this innovative approach aims to increase the probability of the anal preservation with acceptable postoperative outcomes., Materials and Methods: From December 2015 to August 2019, we retrospectively analyzed the short-term outcomes of 12 patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1-3N+M0) primary locally advanced low rectal cancer. They all had received Lap ISR and INTRABEAM IORT with a dose of 16-18 Gy applied by an applicator through the anus (natural orifice). Then, with no pre- or postoperative radiotherapy given, the patients were suggested to receive 6-8 cycles of the XELOX chemotherapy regimen (oxaliplatin, 130 mg/m 2 and capecitabine, 1000 mg/m 2 )., Results: All patients achieved R0 resection. The median radiation time was 27 min and 15 s, and the mean radiative dose was 17.3 Gy (range 16-18 Gy). The median follow-up time was 18.5 months (range 3-45 months). Two patients experienced local recurrence. Two male patients experienced anastomotic stenosis. Furthermore, one of them experienced perianal abscess and the other one experienced pulmonary metastasis after refusing to receive chemotherapy. One female patient with internal anal sphincter invasion experienced distant metastases to the liver and gluteus maximus muscle 35 months after IORT. No acute radiation injuries or symptoms were observed. Although they experienced a reduction in anal function, every patient was satisfied with the postoperative outcomes., Conclusions: For patients evaluated preoperatively with T3 or node-positive (T3N0M0, T1-3N+M0) primary locally advanced low rectal cancer, Lap ISR with INTRABEAM IORT may be a safe and feasible approach for anal preservation without compromising oncological outcomes.

Autosomal dominant polycystic kidney disease (ADPKD) is associated with a number of cellular defects such as hyperproliferation, apoptosis, and dedifferentiation. Mutations in polycystin-1 (PC1) account for ∼85% of ADPKD. Here, we showed that wild-type (WT) or mutant PC1 composed of the last five transmembrane (TM) domains and the C-terminus (termed PC1-5TMC) inhibits cell proliferation and protein translation, as well as the downstream effectors of mTOR, consistent with previous reports. Knockdown of B56 α , a subunit of the protein phosphatase 2A (PP2A) complex, or application of PP2A inhibitor okadaic acid or calyculin A, abolished the inhibitory effect of PC1 and PC1-5TMC on proliferation, indicating that PP2A/B56 α mediates the regulation of cell proliferation by PC1. In addition to the phosphorylated S6 and 4EBP1, B56 α was also downregulated by PC1 and PC1-5TMC. Furthermore, the downregulation of B56 α , which may be mediated by mTOR but not AKT, can account for the dependence of PC1-inhibited proliferation on PP2A., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019 Yan Tang et al.)

Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by mutations in the PKD1 (~85%) or PKD2 (~15%) gene which, respectively, encode polycystin-1 (PC1) and polycystin-2 (PC2). How PC1 regulates cell proliferation and apoptosis has been studied for decades but the underlying mechanisms remain controversial. Protein kinase RNA-activated (PKR) is activated by interferons or double-stranded RNAs, inhibits protein translation, and induces cell apoptosis. In a previous study, we found that PC1 reduces apoptosis through suppressing the PKR/eIF2 α signaling. Whether and how PKR is involved in PC1-inhibited proliferation and protein synthesis remains unknown. Here we found that knockdown of PKR abolishes PC1-inhibited proliferation and translation. Because suppressed PKR-eIF2 α signaling/activity by PC1 would stimulate, rather than inhibit, the proliferation and translation, we examined the effect of dominant negative PKR mutant K296R that has no kinase activity and found that it enhances the inhibition of proliferation and translation by PC1. Thus, our study showed that inhibition of cell proliferation and protein synthesis by PC1 is mediated by the total expression but not the kinase activity of PKR, possibly through physical association.

Background: In order to overcome the shortcomings of laparoscopic intersphincteric resection (Lap ISR), an alternative method of delivering intraoperative radiotherapy by Intrabeam X-rays radiotherapy system (XRS) is proposed in this paper. Intrabeam XRS is a device that uses low-energy X-rays source generated by a mobile controller unit, which is featured in accurate irradiation, reduced complications, and less exposure. The purpose of this study is to discuss the feasibility of Lap ISR with intra-operative radiotherapy using low-energy X-rays for locally advanced ultra-low rectal cancer in Asian woman. This novel proposed method will greatly increase the anus preserving probability and improved the quality of life., Methods: A 53-year-old woman diagnosed with rectal adenocarcinoma had a strong desire to preserve the anal function and presented at the Jilin University Second Hospital, Jilin, China. The tumor's size was 4 cm × 3 cm. It was located 2 cm from the anus merge and invaded the levator ani muscle. Preoperative clinical staging was T4N1M0 and could be reached R0 resection. After the consent form was signed by the patient, Lap ISR combined with the applicator put through the anus (natural orifice) to the tumor bed was performed and prophylactic ileostomy synchronized the anastomosis. Patient only received 1-cycle chemotherapy regimen of oxaliplatin with capecitabine postoperatively due to personal reasons. Pre- or postoperative radiotherapy was not given., Results: After clinical follow-up, until now, there is not any sign of local recurrence. Anus function and short-term complications are acceptable. The short-term effect is satisfying and we look forward to further assess the long-term effect., Conclusion: Laparoscopic intersphincteric resection with IORT using low-energy X-rays for the patients with late-stage ultra-low rectal cancer could provide an opportunity of preserving the anus function, and it is feasible for the selected patients., Trial Registration: Retrospectively registered; Trial registration: NCT03393234 ; Registered time: 05 January 2017.

CRISPR-Cas9 systems are bacterial adaptive immune systems that defend against infection by phages. Through the RNA-guided endonuclease activity of Cas9 they degrade double-stranded DNA with a protospacer adjacent motif (PAM) and sequences complementary to the guide RNA. Recently, two anti-CRISPR proteins (AcrIIA2 and AcrIIA4 from Listeria monocytogenes prophages) were identified, both of which inhibit Streptococcus pyogenes Cas9 (SpyCas9) and L. monocytogenes Cas9 activity in bacteria and human cells. However, the mechanism of AcrIIA2- or AcrIIA4-mediated Cas9 inhibition remains unknown. Here we report a crystal structure of SpyCas9 in complex with a single-guide RNA (sgRNA) and AcrIIA4. Our data show that AcrIIA2 and AcrIIA4 interact with SpyCas9 in a sgRNA-dependent manner. The structure reveals that AcrIIA4 inhibits SpyCas9 activity by structurally mimicking the PAM to occupy the PAM-interacting site in the PAM-interacting domain, thereby blocking recognition of double-stranded DNA substrates by SpyCas9. AcrIIA4 further inhibits the endonuclease activity of SpyCas9 by shielding its RuvC active site. Structural comparison reveals that formation of the AcrIIA4-binding site of SpyCas9 is induced by sgRNA binding. Our study reveals the mechanism of SpyCas9 inhibition by AcrIIA4, providing a structural basis for developing 'off-switch' tools for SpyCas9 to avoid unwanted genome edits within cells and tissues.

To evaluate the antitumor role of genes B7.2 and IL18, the radiation-inducible dual-gene coexpression plasmid pEgr-IL18-B7.2 was constructed and its effects on tumor were detected both in vitro and in vivo. After the introduction of pEgr-IL18-B7.2 into B16 melanoma cells, followed by X-ray irradiation, higher expression levels of B7.2 and IL18 compared with control were found both by flow cytometry and enzyme-linked immunosorbent assay. It was shown that even low-dose irradiation was able to induce their expression, which could be tightly regulated either by giving cells different doses of radiation or the same dose at different time points. pEgr-IL18-B7.2 was then packaged with liposome and injected into melanoma tumor-bearing mice. The tumors received 5 Gy of local X-ray irradiation every other day for a total of five treatments. B16 tumor growth slowed significantly when treated with pEgr-IL18-B7.2 plus X-radiation versus either treatment separately. Both 1 and 3 days after the last irradiation the group of mice with combined gene and radiation therapy showed significantly higher tumor necrosis factor (TNF)-alpha secretion in peritoneal macrophages, upregulated splenic cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and higher interferon (IFN)-gamma secretion than those in either individual treatment group or the control group. The stimulation of host anticancer immunity by increased secretion of IL-18 and upregulated immunogenicity of the tumor cells by increased expression of B7.2 on their surface, in addition to the direct effect of local X-irradiation on the tumor cells, may contribute to the novel effect of the combined therapy.