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Abstract We investigated a time-delayed optoelectronic oscillator (OEO) that displays a wide range of complex dynamic behavior under small time delay. The phase-space trajectory distributions in different dynamic regimes were compared which brings a new perspective on the underlying mechanism of the transition process. It was found that bifurcation is always possible no matter how small the time delay is even if the universal adiabatic approximation model is invalid. Hereby we proposed a versatile simple oscillator which has a potential capacity as memory carrier and high-dimensional state spatial mapping ability that brings 1000 times computing-efficiency improvements of reservoir computing over the large time delay one. Furthermore, we demonstrated a new approach for a tunable optoelectronic pulse generator (repetition rate at 0.2 MHz and 0.25 GHz) which depends critically on time-delayed input electrical pulse. The proposed oscillator is also a promising system for the applications of fast chaos-based communication.

Blood-brain barrier (BBB) breakdown is a critical event in cerebral ischemia-reperfusion (I/R) injury, and matrix metalloproteinases (MMPs), which are proteolytic enzymes, play essential roles in BBB breakdown through degrading the extracellular matrix. N6-Methyladenosine (m6A), the most common and reversible mRNA modification, has an important role in the progression of cerebral I/R injury. However, whether m6A is related to BBB breakdown and MMPs expression in cerebral I/R injury is still not clear. In this study, we explored the potential effects of m6A modification on BBB breakdown in cerebral I/R injury and its underlying mechanisms using mice subjected to transient middle cerebral artery occlusion and reperfusion (MCAO/R), and mouse brain endothelial cells treated with oxygen-glucose deprivation and reoxygenation (OGD/R). We find that MMP3 expression is highly expressed and positively associated with the m6A writer CBLL1 (Cbl proto-oncogene like 1) in cerebral I/R injury in vivo and in vitro. Furthermore, MMP3 mRNA occurs m6A modification in mouse brain endothelial cells, and the m6A modification level of MMP3 mRNA is significantly increased in cerebral I/R injury. Moreover, inhibition of m6A modification reduces MMP3 expression and ameliorates BBB breakdown in cerebral I/R in vivo and in vitro. In conclusion, m6A modification promotes BBB breakdown in cerebral I/R injury through increasing MMP3 expression, indicating that m6A may be a potential therapeutic target for cerebral I/R injury.

Abstract Coherent optical control of the magnetization in ferromagnetic (FM) mediums using ultrafast nonthermal effect paves a promising avenue to improve the speed and repetition rate of the magnetization manipulation. Whereas previously, only heat‐induced or helicity‐dependent magnetization dynamics are demonstrated in metallic ferromagnets. Here, the linearly‐polarized light control of magnetization is demonstrated in FM Co coupled with ferroelectric (FE) BiFeO3 by tuning the light polarization direction. It is revealed that in the Co/BiFeO3 heterostructure excited by femtosecond laser pulses, the magnetization precession amplitude follows a sinusoidal dependence on the laser polarization direction. This nonthermal control of coherent magnetization rotation is attributed to the optical rectification effect in the BiFeO3 layer, which yields a FE polarization depending on the light polarization, and the subsequent modulation of magnetic energy in Co by the electrostriction‐induced strain. This work demonstrates an effective route to nonthermally manipulate the ultrafast magnetization dynamics in metallic ferromagnets.

Currently, there is a shortage of pediatric medicines on the market, and 3D printing technology can more flexibly produce personalized medicines to meet individual needs. The study developed a child-friendly composite gel ink (carrageenan-gelatin), created 3D models by computer-aided design technology, then produced personalized medicines using 3D printing to improve the safety and accuracy of medication for pediatric patients. An in-depth understanding of the printability of different formulations was obtained by analyzing the rheological and textural properties of different gel inks and observing the microstructure of different gel inks, which guided the formulation optimization. Through formulation optimization, the printability and thermal stability of gel ink were improved, and F6 formulation (carrageenan: 0.65%; gelatin: 12%) was selected as the 3D printing inks. Additionally, a personalized dose linear model was established with the F6 formulation for the production of 3D printed personalized tablets. Moreover, the dissolution tests showed that the 3D printed tablets were able to dissolve more than 85% within 30 min and had similar dissolution profiles to the commercially available tablets. This study demonstrates that 3D printing is an effective manufacturing technique that allows for flexible, rapid, and automated production of personalized formulations.

Recently, the development of Binder Jet 3D printing technology has promoted the research and application of personalized formulations, which are especially useful for children’s medications. Additionally, physiological pharmacokinetic (PBPK) modeling can be used to guide drug development and drug dose selection. Multiple technologies can be used in combination to increase the safety and effectiveness of drug administration. In this study, we performed in vivo pharmacokinetic experiments in dogs with preprepared 3D-printed levetiracetam instant-dissolving tablets (LEV-IDTs). Bioequivalence analysis showed that the tablets were bioequivalent to commercially available preparations (Spritam®) for dogs. Additionally, we evaluated the bioequivalence of 3D-printed LEV-IDTs with Spritam® by a population-based simulation based on the established PBPK model of levetiracetam for Chinese adults. Finally, we established a PBPK model of oral levetiracetam in Chinese children by combining the physiological parameters of children, and we simulated the PK (pharmacokinetics) curves of Chinese children aged 4 and 6 years that were administered the drug to provide precise guidance on adjusting the dose according to the effective dose range of the drug. Briefly, utilizing both Binder jet 3D printing technology and PBPK models is a promising route for personalized drug delivery with various age groups.

Abstract Objective Adjuvant chemotherapy is necessary for radical resection of intrahepatic cholangiocarcinoma (ICC) with a high risk of recurrence (T2–4, N1). However, its use in the treatment of early-stage ICC remains controversial. This study aimed to investigate the role of adjuvant chemotherapy after radical resection in patients with early-stage ICC (T1N0M0). Data and methods The data of 148 patients with pathologically diagnosed ICC (T1N0M0) who underwent radical resection from January 2012 to January 2018 at the Sun Yat-sen University Cancer Center were retrospectively analyzed. Using consistent baseline data, Kaplan–Meier survival curves were constructed to compare relapse-free survival (RFS) and overall survival (OS) between patients who received postoperative adjuvant chemotherapy (AC group) and those who received only surgical treatment (non-AC group). Univariate and multivariate Cox regression analyses were used to screen for independent prognostic factors affecting survival. The RFS and OS of patients were analyzed after the administration of three adjuvant chemotherapy regimens (gemcitabine + capecitabine [GX], gemcitabine + cisplatin [GP], and capecitabine monotherapy [X]). Finally, the safety of adjuvant chemotherapy was evaluated based on the incidence of grade 1–4 adverse events. Results The median RFS was 18 months in the non-AC group and 25 months in the AC group. The median OS was 34 months in the non-AC group; however, it was not reached in the AC group. The OS of the AC group was significantly higher than that of the non-AC group (P = 0.005). Multivariate Cox analysis demonstrated that nerve invasion (P = 0.001), preoperative elevation of cancer antigen 19–9 (CA 19–9) levels (P = 0.009), and postoperative adjuvant chemotherapy (P = 0.009) were independent prognostic factors for early-stage ICC after radical resection. The OS rates of the GX, GP, X, and non-AC groups were significantly different (P = 0.023) and were higher in the GX group than in the non-AC group (P = 0.0052). Among patients with elevated preoperative CA 19–9 levels, the OS rate was higher in the AC group than in the non-AC group (P = 0.022). In terms of safety, the incidence of grade 3 or 4 adverse reactions was

Food‐derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non‐gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non‐gastrointestinal diseases via the gut‐liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut‐liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non‐alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut‐liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases. [ABSTRACT FROM AUTHOR]

AIM: To investigate the incidence and risk factors of near vision impairment(NVI)in patients with asthenopia.METHODS: Totally 51 patients(102 eyes)with visual fatigue in our hospital from May 2017 to May 2018 were enrolled. According to whether the near vision of daily life is damaged, it is divided into daily near vision impairment group(24 cases)and no near vision impairment group(27 cases). General information of all patients were collected, and routine eye examination, subjective optometry and binocular eye movement parameter detection were detected.RESULTS: In the survey, 27 patients(53%)with near vision impairment in naked eye and 24 patients(47%)with impaired near vision in daily life, and all patients had a significant improvement in visual acuity after correct optometry, and there was no one who has best corrected near visual acuity impairment. The age of patients with daily near vision impairment was significantly higher than that of patients without near vision impairment. The proportion of patients aged ≥45 years was significantly higher than that without near vision impairment(PPCONCLUSION: Nearly half of patients with asthenopia would suffer NVI. The increase of age and imbalance between NRA and PRA as the predominant risk factors for its development.

Abstract Background To evaluate the perioperative and long-term results of intrahepatic bile duct exploration lithotomy (IHBDIL) combined with hepatectomy for patients with complicated bilateral primary hepatolithiasis. Methods A study was conducted involving 56 patients with complicated bilateral primary hepatolithiasis who underwent IHBDIL combined with hepatectomy at our hospital from January 2006 to December 2014. The perioperative and long-term outcomes that were retrospectively analysed included the stone clearance rate, operative morbidity and mortality, and stone recurrence rate. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded. Results In all 56 patients, hepatic duct stones were located in the bilateral IHBD. The surgical method was IHBDIL combined with hepatectomy. Postoperative complications occurred in 15 patients (26.8%), 14 patients responded to conservative management, and there was 1 case of postoperative mortality because of hepatic failure. The overall initial success rate of stone clearance was 85.7%, and the final clearance rate was 92.9% following postoperative choledochoscopic lithotripsy. The stone recurrence rate was 13.5%, and the occurrence of postoperative cholangitis was 10.9% during the follow-up period. Conclusion IHBDIL combined with hepatectomy is a safe, effective, and promising treatment for patients with complicated bilateral primary hepatolithiasis. The perioperative and long-term outcomes are satisfactory for complicated bilateral primary hepatolithiasis.

We investigated the variation in microbial community and fermentation characteristics of whole-plant corn silage after treatment with lactic acid bacteria (LAB) and organic acids. The fresh corn forages were treated with a combination of L. acidophilus and L. plantarum (106 CFU/g fresh material) or a 7:1:2 ratio of formic acid, acetic acid, and propionic acid (6 mL/g fresh material) followed by 45 or 90 days of ensiling. Silages treated with LAB showed increased lactic acid content and decreased pH after 45 days. Although treatment with LAB or organic acids decreased the common and unique operational taxonomic units, indicating a reduction in microbial diversity, the relative abundance of Lactobacillus was elevated after 45 and 90 days compared with control, which was more distinct in the organic acid groups. Moreover, we found higher levels of acetic acid and increased abundance of Acetobacter in silages treated with organic acids whereas undesirable microorganisms such as Klebsiella, Paenibacillus, and Enterobacter were reduced. In summary, the quality of corn silages was improved by LAB or organic acid treatment in which LAB more effectively enhanced lactic acid content and reduced pH while organic acid inhibited the growth of undesirable microorganisms.

The study was conducted to compare and analyze the nutritional value of different protein feed materials. Ten kinds of protein feeds (soybean meal, palm meal, cottonseed meal, monosodium glutamate meal, sesame cake meal, sunflower meal, distillers dried grains with solubles, peony seed meal, beer grains, and soybean residue) were collected from beef cattle farms with three replicates for each feed. The carbohydrate composition, protein composition, amino acid composition, and predicted em-value indexes were determined and analyzed. The results showed that the CHO content of soybean residue was the highest (73.78%), followed by peony seed meal (66.76%) and palm meal (65.89%). The NSC content of monosodium glutamate residue and soybean meal was higher, while the CC content was lower. The CP content of monosodium glutamate residue, soybean meal, sesame cake, and cottonseed meal was higher than 50%, significantly higher than other materials (P<0.05). The PA content and PB1 content of monosodium glutamate residue and peony seed meal were significantly higher than other materials (P<0.05). The EAA and Lys contentrations of soybean meal, monosodium glutamate residue, and cottonseed meal were higher than other materials (P<0.05). The TDN content of corn alcohol grains, monosodium glutamate residue, peony seed meal, and sesame cake meal was higher than 80%. NEg and NEL showed the same trend as TDN. The study indicates that the nutritional content of different protein feed materials is significantly different. Considering the protein components and energy value, the nutritional value of monosodium glutamate residue, cottonseed meal, and sesame cake are equivalent to that of soybean meal, and they have obvious advantages to replacing soybean meal in production. [ABSTRACT FROM AUTHOR]

1000 YEARS OF JOYS AND SORROWS The story of two lives, one nation, and a century of art under tyranny AI WEIWEI 400pp. Bodley Head. 25 [pounds sterling]. When Ai [...]

SHUNA'S JOURNEY HAYAO MIYAZAKI Translated by Alex Dudok de Wit 160pp. St Martin's Press. 21.99 [pounds sterling]. There's a viral clip that periodically resurfaces on my Twitter feed: the artist [...]

The article "Addressing parental bereavement after suicide: Insights and initiatives from Taiwan" discusses the experiences of parents who have lost a child to suicide, highlighting the profound grief and existential suffering they endure. The study emphasizes the need for long-term, trauma-informed professional support for suicide-bereaved parents, with initiatives such as suicide prevention task forces, comprehensive risk assessment, staff training, and community outreach programs in place at the Taoyuan Psychiatric Center in Taiwan. The authors stress the importance of ongoing research, education, and service development to better support individuals and families affected by suicide, calling for a comprehensive, systemic approach to suicide prevention. [Extracted from the article]