Cryogenic Electron-Beam Writing for Perovskite Metasurface.

Halide perovskites (HPs) metasurfaces have recently attracted significant interest due to their potential to not only further enhance device performance but also reveal the unprecedented functionalities and novel photophysical properties of HPs. However, nanopatterning on HPs is critically challenging as they are readily destructed by the organic solvents in the standard lithographic processes. Here, we present a novel, subtle, and fully nondestructive HPs metasurface fabrication strategy based on cryogenic electron-beam writing. This technique allows for high-precision patterning and in situ imaging of HPs with excellent compatibility. As a proof-of-concept, broadband absorption enhanced metasurfaces were realized by patterning nanopillar arrays on CH3NH3PbI3 film, which results in photodetectors with approximately 14-times improvement on responsivity and excellent stability. Our findings highlight the great feasibility of cryogenic electron-beam writing for producing perovskite metasurface and unlocking the unprecedented photoelectronic properties of HPs.

Effect of short-term nitrogen deposition on dry-wet seasonal variation of soil respiration in degraded Poa pratensis alpine meadow of the Napahai, Yunnan, China.

To explore the coupling of dry-wet seasonal variations of soil respiration with their environmental factors in the alpine meadow under the background of increasing nitrogen (N) deposition, we conducted an experiment in the typical degraded Poa pratensis meadow in the Napahai, Yunnan. There were four treatments, i.e., control (0 g·m-2·a-1), low (5 g·m-2·a-1), medium (10 g·m-2·a-1), and high (15 g·m-2·a-1) levels. We examined the effects of aboveground biomass, plant diversity, and soil physicochemical properties on soil respiration. The results showed that N deposition significantly promoted soil respiration. Compared with that in the control, soil respiration rates increased by 21.9%-53.9% and 27.3%-51.2% in dry and wet seasons, respectively. The maximum value of soil respiration rate was recorded in the medium N treatment. N deposition dramatically elevated aboveground biomass (52.2%-66.4%). Plant diversity declined with increasing N addition levels, with the maximum value (13.5%-24.2%) being recorded in high treatment in wet season. The values of ammonium nitrogen, organic matter, microbial biomass carbon and nitrogen, temperature and moisture in the three N treatments were elevated by 14.3%-333.5% compared with the control, while those of soil pH were decreased by 9.0%-34.6%. Results of the structural equation modelling showed that plant biomass, Shannon diversity, microbial biomass, soil temperature, and moisture showed a positive effect on soil respiration, while bulk density had a negative effect. Soil nitrogen pool and pH were main factors driving soil CO2 emissions, accounting for 55.7% and 45.1% of the variations, respectively. Therefore, short-term atmospheric N deposition stimulated soil respiration primarily via altering soil pH and nitrogen pool components in the degraded alpine meadow.

Precise large-fragment deletions in mammalian cells and mice generated by dCas9-controlled CRISPR/Cas3.

Currently, the Cas9 and Cas12a systems are widely used for genome editing, but their ability to precisely generate large chromosome fragment deletions is limited. Type I-E CRISPR mediates broad and unidirectional DNA degradation, but controlling the size of Cas3-mediated DNA deletions has proven elusive thus far. Here, we demonstrate that the endonuclease deactivation of Cas9 (dCas9) can precisely control Cas3-mediated large-fragment deletions in mammalian cells. In addition, we report the elimination of the Y chromosome and precise retention of the Sry gene in mice using CRISPR/Cas3 and dCas9-controlled CRISPR/Cas3, respectively. In conclusion, dCas9-controlled CRISPR/Cas3-mediated precise large-fragment deletion provides an approach for establishing animal models by chromosome elimination. This method also holds promise as a potential therapeutic strategy for treating fragment mutations or human aneuploidy diseases that involve additional chromosomes.

Online legal driving behavior monitoring for self-driving vehicles.

Defined traffic laws must be respected by all vehicles when driving on the road, including self-driving vehicles without human drivers. Nevertheless, the ambiguity of human-oriented traffic laws, particularly compliance thresholds, poses a significant challenge to the implementation of regulations on self-driving vehicles, especially in detecting illegal driving behaviors. To address these challenges, here we present a trigger-based hierarchical online monitor for self-assessment of driving behavior, which aims to improve the rationality and real-time performance of the monitoring results. Furthermore, the general principle to determine the ambiguous compliance threshold based on real driving behaviors is proposed, and the specific outcomes and sensitivity of the compliance threshold selection are analyzed. In this work, the effectiveness and real-time capability of the online monitor were verified using both Chinese human driving behavior datasets and real vehicle field tests, indicating the potential for implementing regulations in self-driving vehicles for online monitoring.

Effectiveness of the "Hand as Foot" teaching method in human physiology: A randomized controlled trial.

BACKGROUND: The "Hand as Foot" teaching method, an innovative approach in medical education, utilizes hand gestures to simulate anatomical structures and functions. This study aimed to assess the effectiveness of the "Hand as Foot" teaching method compared to traditional method in the "Human Physiology" course. METHODS: During the 2023 spring semester, a randomized controlled trial involved 84 health management students. Participants were randomly assigned to the "Hand as Foot" teaching group or the traditional teaching group. A self-designed Likert scale was used to evaluate students' perceptions of teaching effectiveness, covering dimensions such as engagingness, intuitiveness, facilitation of understanding, enhancement of memorization, and effortlessness of learning. Additionally, a knowledge assessment test was administered to measure knowledge acquisition. RESULTS: The "Hand as Foot teaching method" group (41 students) reported significantly higher ratings for all dimensions of teaching effectiveness compared to the traditional teaching group (43 students) (p ≤ 0.01). Despite the lack of statistical significance, the experimental group's test scores were notably superior (Mean = 6.35 vs. Mean = 5.94). DISCUSSION: The "Hand as Foot" teaching method demonstrated superior effectiveness in engaging students, facilitating comprehension, and enhancing memorization. Its interactive and tangible nature provided a holistic learning experience, enabling students to visualize complex physiological mechanisms. Additionally, it fostered active student participation and a desire for deeper understanding. CONCLUSION: While the "Hand as Foot" teaching method demonstrated strengths in engaging students and aiding comprehension, further researches with larger and diverse cohorts are needed to gauge its impact on learning outcomes and broader applicability.

Bone Organoids: Recent Advances and Future Challenges.

Bone defects stemming from tumorous growths, traumatic events, and diverse conditions present a profound conundrum in clinical practice and research. While bone has the inherent ability to regenerate, substantial bone anomalies require bone regeneration techniques. Bone organoids represent a new concept in this field, involving the 3D self-assembly of bone-associated stem cells guided in vitro with or without extracellular matrix material, resulting in a tissue that mimics the structural, functional, and genetic properties of native bone tissue. Within the scientific panorama, bone organoids ascend to an esteemed status, securing significant experimental endorsement. Through a synthesis of current literature and pioneering studies, this review offers a comprehensive survey of the bone organoid paradigm, delves into the quintessential architecture and ontogeny of bone, and highlights the latest progress in bone organoid fabrication. Further, existing challenges and prospective directions for future research are identified, advocating for interdisciplinary collaboration to fully harness the potential of this burgeoning domain. Conclusively, as bone organoid technology continues to mature, its implications for both clinical and research landscapes are poised to be profound.

Event-triggered low-computation adaptive output-feedback fuzzy tracking control of uncertain nonlinear systems.

A fuzzy adaptive tracking control scheme is studied for a family of uncertain systems with immeasurable system states. The controller takes up few computation and transmission resources to achieve prescribed boundaries of the dynamic and steady-state performance indicators. Compared with the existing schemes, the low computational complexity is reflected in the following two points: (1) a fuzzy state observer is introduced, where only the estimation of states are incorporated into the input space of fuzzy logic systems (FLSs). (2) The problem of complexity explosion can be avoided without utilizing additional command filters or auxiliary dynamic surface control techniques. In addition, using the event-triggered control scheme, the data in the transmission is significantly reduced. Finally, the effectiveness of the scheme is fully verified by simulation.

Efficacy and safety of autologous platelet-rich plasma for diabetic foot ulcers: a systematic review and meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of autologous platelet-rich plasma (au-PRP) for diabetic foot ulcer (DFU) treatment. METHOD: We conducted database searches (MEDLINE, EMBASE, evidence-based medicine reviews: CENTRAL, PubMed, and Web of Science) and reference mining for randomised controlled trials from inception to 23 January 2022. Results were scrutinised, data were extracted and research quality was investigated by two independent authors. Primary outcome was the proportion of complete ulcer healing. Secondary outcomes included both the mean time to complete healing and the incidence of adverse events. Statistical analyses were performed in RevMan 5.4 (Cochrane, UK). Kaplan-Meier curves for time to complete healing were pooled in R software (version 4.1.2) (R Foundation, Austria). RESULTS: Of the 231 records identified, 17 studies with a total of 1303 participants (649 randomised to the au-PRP group and 654 to a standard of care (SOC) group) met the eligibility criteria and were included in our study. Compared with SOC, au-PRP appeared to promote the complete healing rate (odds ratio (OR): 2.11; 95% Confidence Interval: 1.55-2.86). Au-PRP also appeared to significantly shorten complete healing time (mean duration: -19.04 days; 95%CI: -20.46--17.61]). There was no significant difference on adverse events. Results were robust on sensitivity analyses. CONCLUSION: Based on the findings of this review and meta-analysis, Au-PRP is an effective and safe adjuvant therapy for DFUs.

Engineered domain-inlaid Nme2Cas9 adenine base editors with increased on-target DNA editing and targeting scope.

BACKGROUND: Nme2ABE8e has been constructed and characterized as a compact, accurate adenine base editor with a less restrictive dinucleotide protospacer-adjacent motif (PAM: N4CC) but low editing efficiency at challenging loci in human cells. Here, we engineered a subset of domain-inlaid Nme2Cas9 base editors to bring the deaminase domain closer to the nontarget strand to improve editing efficiency. RESULTS: Our results demonstrated that Nme2ABE8e-797 with adenine deaminase inserted between amino acids 797 and 798 has a significantly increased editing efficiency with a wide editing window ranging from 4 to 18 bases in mammalian cells, especially at the sites that were difficult to edit by Nme2ABE8e. In addition, by swapping the PAM-interacting domain of Nme2ABE8e-797 with that of SmuCas9 or introducing point mutations of eNme2-C in Nme2ABE8e-797, we created Nme2ABE8e-797Smu and Nme2ABE8e-797-C, respectively, which exhibited robust activities at a wide range of sites with N4CN PAMs in human cells. Moreover, the modified domain-inlaid Nme2ABE8e can efficiently restore or install disease-related loci in Neuro-2a cells and mice. CONCLUSIONS: These novel Nme2ABE8es with increased on-target DNA editing and expanded PAM compatibility will expand the base editing toolset for efficient gene modification and therapeutic applications.

Development of a highly efficient prime editor system in mice and rabbits.

The recently developed prime-editing (PE) technique is more precise than previously available techniques and permits base-to-base conversion, replacement, and insertions and deletions in the genome. However, previous reports show that the efficiency of prime editing is insufficient to produce genome-edited animals. In fact, prime-guide RNA (pegRNA) designs have posed a challenge in achieving favorable editing efficiency. Here, we designed prime binding sites (PBS) with a melting temperature (Tm) of 42 °C, leading to optimal performance in cells, and we found that the optimal Tm was affected by the culture temperature. In addition, the ePE3max system was developed by updating the PE architecture to PEmax and expressing engineered pegRNA (epegRNA) based on the original PE3 system. The updated ePE3max system can efficiently induce gene editing in mouse and rabbit embryos. Furthermore, we successfully generated a Hoxd13 (c. 671 G > T) mutation in mice and a Tyr (c. 572 del) mutation in rabbits by ePE3max. Overall, the editing efficiency of modified ePE3max systems is superior to that of the original PE3 system in producing genome-edited animals, which can serve as an effective and versatile genome-editing tool for precise genome modification in animal models.

A new compact adenine base editor generated through deletion of HNH and REC2 domain of SpCas9.

BACKGROUND: Adenine base editors (ABEs) are promising therapeutic gene editing tools that can efficiently convert targeted A•T to G•C base pairs in the genome. However, the large size of commonly used ABEs based on SpCas9 hinders its delivery in vivo using certain vectors such as adeno-associated virus (AAV) during preclinical applications. Despite a number of approaches having previously been attempted to overcome that challenge, including split Cas9-derived and numerous domain-deleted versions of editors, whether base editor (BE) and prime editor (PE) systems can also allow deletion of those domains remains to be proven. In this study, we present a new small ABE (sABE) with significantly reduced size. RESULTS: We discovered that ABE8e can tolerate large single deletions in the REC2 (Δ174-296) and HNH (Δ786-855) domains of SpCas9, and these deletions can be stacked together to create a new sABE. The sABE showed higher precision than the original ABE8e, with proximally shifted protospacer adjacent motif (PAM) editing windows (A3- A15), and comparable editing efficiencies to 8e-SaCas9-KKH. The sABE system efficiently generated A-G mutations at disease-relevant loci (T1214C in GAA and A494G in MFN2) in HEK293T cells and several canonical Pcsk9 splice sites in N2a cells. Moreover, the sABE enabled in vivo delivery in a single adeno-associated virus (AAV) vector with slight efficiency. Furthermore, we also successfully edited the genome of mouse embryos by microinjecting mRNA and sgRNA of sABE system into zygotes. CONCLUSIONS: We have developed a substantially smaller sABE system that expands the targeting scope and offers higher precision of genome editing. Our findings suggest that the sABE system holds great therapeutic potential in preclinical applications.

The emotional facial recognition performance of Chinese patients with schizophrenia: An event-related potentials study.

Background: Patients with schizophrenia have deficits in identifying and recognizing emotional facial expressions. Aim: This study aimed to explore the event-related potential (ERP) responses of patients with schizophrenia (SZ) and healthy controls (HC) using the Chinese Facial Affective Picture System (CFAPS). Methods: This study included 30 SZs and 31 HCs. We asked them to complete the task based on the oddball paradigm, in which three emotional faces (happy, fearful, and neutral) were used as target stimuli. Additionally, the amplitude and latency of the N170 component and the P300 component were recorded synchronously. Results: Compared with HCs, SZs had significantly smaller amplitudes of N170 and P300 to all facial expressions. The pairwise comparison revealed that fearful faces could trigger a significantly larger P300 amplitude in HCs than neutral faces, while the such a difference was not found in SZs. Conclusion: These findings indicated that SZs had a noticeable deficiency in the structural coding of face recognition and available attentional resources.

Partial trisomy 9p and partial monosomy 7p of an infant inherited from maternal balanced translocation: a case report.

BACKGROUND: Subchromosomal deletions and duplications are the leading cause of congenital malformations and mental retardation in children. With the recent clinical application of genomic microarrays in the evaluation of patients with developmental delays and congenital malformations, it has led to the discovery of several new microdeletion and microduplication syndromes. However, there are no published reports involving patients with both microduplications in the 9p21.1-p24.3 region and microdeletions in the 7p22.1-p22.3 region. CASE PRESENTATION: We report an infant with an autosomal abnormality confirmed by conventional karyotype combined with copy number variations sequencing (CNV-seq), showing the patient with an unbalanced translocation. The karyotype of the patient was 46, XX, der (7)t (7;9) (p22; p21) and CNV-seq results showed an approximately 32.34-Mb duplication in 9p21.1-p24.3 (200000-32540000) and an approximately 3.3-Mb deletion in 7p22.2-p22.3 (40000-3340000). CONCLUSIONS: The patient carried an unbalanced translocation 46, XX, der (7)t (7;9) (p22; p21) derived from her mother. The clinical presentation is closely related to the size and position of the missing and duplicated chromosomes. To our knowledge, the simultaneous occurrence of de novo partial trisomy 9p(9p21.1-p24.3) and partial monosomy 7p (7p22.2-p22.3) has not previously been reported up until now. The present study additionally demonstrated that CNV-seq combined with karyotype is able to reliably detect unbalanced submicroscopic chromosomal aberrations.

Berberine ameliorates the neurological dysfunction of the gastric fundus by promoting calcium channels dependent release of ACh in STZ-induced diabetic rats.

Background: It has been reported diabetic gastroparesis is related to diabetic autonomic neuropathy of the gastrointestinal tract, and berberine (BBR) could ameliorate diabetic central and peripheral neuropathy. However, the influence of BBR on the function and motility of the gastric fundus nerve is unclear. Methods: A diabetic rat model was constructed, and HE staining was used to observe the morphological changes in the gastric fundus. The changes in cholinergic and nitrogen-related neurochemical indexes and the effects of BBR on them were measured using Elisa. The effects of BBR on the neural function and motility of gastric fundus were investigated by electric field stimulation (EFS) induced neurogenic response in vitro. Results: In the early stage of STZ-induced diabetic rats, the contractile response of gastric fundus induced by EFS was disorder, disturbance of contraction amplitude, and the cell bodies of neurons in the myenteric plexus of gastric fundus presented vacuolar lesions. Administration with BBR could improve the above symptoms. BBR further enhanced the contraction response in the presence of a NOS inhibitor or the case of inhibitory neurotransmitters removal. Interestingly, the activity of ACh could affect NO release directly and the enhancement of BBR on contractile response was canceled by calcium channel blockers completely. Conclusions: In the early stage of STZ-induced diabetic rats, the neurogenic contractile response disorder of the gastric fundus is mainly related to cholinergic and nitrergic nerve dysfunction. BBR promotes the release of ACh mainly by affecting the calcium channel to improve the neurological dysfunction of the gastric fundus.

 Sinoseneciominshanicus (Asteraceae, Senecioneae), a new species from south-eastern Gansu and northern Sichuan, China.

Sinoseneciominshanicus (Asteraceae, Senecioneae), a new species from south-eastern Gansu (Wenxian and Zhugqu counties) and northern Sichuan (Pingwu county), China, is described and illustrated. This species is similar to S.rotundifolius, a species locally endemic to Songpan county in northern Sichuan, in having a scapigerous habit, orbicular leaves and solitary capitula, but differs by the presence (vs. absence) of stolons and by having thinner rhizomes (ca. 2 mm vs. more than 5 mm in diameter), stems proximally sparsely fulvous arachnoid or glabrescent (vs. densely sericeous-villous) and obscure (vs. conspicuous) main veins on adaxial surface of leaves. The chromosome number of the new species is reported to be 2n = 60. Colour photographs of living plants in the wild and a distribution map are provided for the new species and S.rotundifolius. The geographical distribution of S.rotundifolius is also corrected, with the previous record of this species from south-eastern Gansu (Wenxian county) actually referring to S.minshanicus.

Sinoseneciopingwuensis (Asteraceae, Senecioneae), a new species from northern Sichuan, China.

Sinoseneciopingwuensis (Asteraceae, Senecioneae), a new species from Pingwu county in northern Sichuan, China, is described and illustrated. This species is distinguished in Sinosenecio by having leathery, glabrous, ovate or ovate-oblong leaves often pinnately-veined and solitary capitula 2.3-4.3 cm in diameter, a unique character combination hitherto never recorded in the genus. Two floral micromorphological characters (configuration of filament collar of stamens and anther endothecial cell wall thickenings) and achene surface features of the new species are reported. Color photographs of living plants and a distribution map are also provided for the new species.

Production and Patterning of Fluorescent Quantum Dots by Cryogenic Electron-Beam Writing.

Graphene quantum dots (GQDs) have emerged as a promising type of functional material with distinguished properties. Although tremendous effort was devoted to the preparation of GQDs, their applications are still limited due to a lack of methods for processing GQDs from synthesis to patterning smoothly. Here, we demonstrate that aromatic molecules, e.g., anisole, can be directly converted into GQD-containing nanostructures by cryogenic electron-beam writing. Such an electron-beam irradiation product exhibits evenly red fluorescence emission under laser excitation at 473 nm, and its photoluminescence intensity can be easily tuned with the electron-beam exposure dose. Experimental characterizations on the chemical composition of the product reveal that anisole undergoes a carbonization and further graphitization process during e-beam irradiation. With conformal coating of anisole, our approach can create arbitrary fluorescent patterns on both planar and curved surfaces for concealing information or anticounterfeiting applications. This study provides a one-step method for production and patterning of GQDs, facilitating their applications in highly integrated and compact optoelectronic devices.