The emergence of machine learning force fields in drug design.

In the field of molecular simulation for drug design, traditional molecular mechanic force fields and quantum chemical theories have been instrumental but limited in terms of scalability and computational efficiency. To overcome these limitations, machine learning force fields (MLFFs) have emerged as a powerful tool capable of balancing accuracy with efficiency. MLFFs rely on the relationship between molecular structures and potential energy, bypassing the need for a preconceived notion of interaction representations. Their accuracy depends on the machine learning models used, and the quality and volume of training data sets. With recent advances in equivariant neural networks and high-quality datasets, MLFFs have significantly improved their performance. This review explores MLFFs, emphasizing their potential in drug design. It elucidates MLFF principles, provides development and validation guidelines, and highlights successful MLFF implementations. It also addresses potential challenges in developing and applying MLFFs. The review concludes by illuminating the path ahead for MLFFs, outlining the challenges to be overcome and the opportunities to be harnessed. This inspires researchers to embrace MLFFs in their investigations as a new tool to perform molecular simulations in drug design.

Protein Allostery Study in Cells Using NMR Spectroscopy.

Protein allostery is commonly observed in vitro. But how protein allostery behaves in cells is unknown. In this work, a protein monomer-dimer equilibrium system was built with the allosteric effect on the binding characterized using NMR spectroscopy through mutations away from the dimer interface. A chemical shift linear fitting method was developed that enabled us to accurately determine the dissociation constant. A total of 28 allosteric mutations were prepared and grouped to negative allosteric, nonallosteric, and positive allosteric modulators. ∼ 50% of mutations displayed the allosteric-state changes when moving from a buffered solution into cells. For example, there were no positive allosteric modulators in the buffered solution but eight in cells. The change in protein allostery is correlated with the interactions between the protein and the cellular environment. These interactions presumably drive the surrounding macromolecules in cells to transiently bind to the monomer and dimer mutational sites and change the free energies of the two species differently which generate new allosteric effects. These surrounding macromolecules create a new protein allostery pathway that is only present in cells.

Chemical composition and absorption characteristics of Raw and Prepared Cassiae Semen extracts based on ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry.

In traditional Chinese medicine, the two commodity forms of Cassiae Semen Raw and Prepared Cassiae Semen, exert different clinical applications, in which Prepared Cassiae Semen is commonly used to treat liver and eye diseases. However, the material basis of Raw and Prepared Cassiae Semen remains unclear due to the limited studies on their overall composition and metabolism in vivo. In this study, an integrated analysis strategy based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry was established to systematically screen the prototype and metabolite constituents of Raw and Prepared Cassiae Semen. Automatic matching analysis of metabolites was performed on Compound Discoverer software based on the function of predicting metabolites. Using this strategy, a total of 77 compounds in Raw Cassiae Semen and 71 compounds in Prepared Cassiae Semen were identified. Furthermore, in vivo study, 46 prototype components and 104 metabolites from the Raw Cassiae Semen group and 41 prototype components and 87 metabolites from the Prepared Cassiae Semen group were unambiguously or preliminarily identified in mice (plasma, urine, feces, eye, and liver). This is the first study of chemical component analysis and in vivo metabolite profiling of Raw and Prepared Cassiae Semen.

Is switching intravesical chemotherapeutic agents beneficial in short-term recurrent high-risk non-muscle-invasive bladder tumors? A 5-year retrospective study.

OBJECTIVE: To explore if switching intravesical chemotherapeutic agents is beneficial in short-term recurrences of high-risk non-muscle-invasive bladder cancer (NMIBC) following the failure of preceding intravesical therapy. MATERIALS AND METHODS: From June 2010 to October 2015, 205 patients with NMIBC who experienced tumor recurrence within a year after receiving first-line intravesical chemotherapy (IVC) were classified into two groups. After a second complete transurethral resection (TUR) process, we immediately altered the intravesical instillation agent for 107 patients (group A). In contrast, the remaining 98 patients (group B) continued using their original intravesical instillation agent. After transurethral resection of the bladder tumor (TURBT), all patients received either an immediate instillation of epirubicin (EPI), gemcitabine (GEM), or hydroxycamptothecin (HCPT), followed by regular induction and maintenance instillations. Recurrence and progression rates were evaluated using the Chi-square test, and recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, there was no significant difference in either the 5-year tumor recurrence or progression rates between the two groups (p > 0.05) The Kaplan-Meier plot showed no difference in progression-free or recurrence-free survival between the two groups. CONCLUSION: Switching IVC agents does not improve RFS and PFS for patients with short-term recurrent high-risk NMIBC.

Medical Adhesive-related Skin Injuries Caused by Eye Taping: A Case Report.

This case report discusses medical adhesive-related skin injuries (MARSIs) caused by eye taping during an emergency open reduction internal fixation surgery under general anesthesia. The presented case involves a 72-year-old woman with a proximal humeral fracture, where 3M Transpore adhesive tape caused blisters on both eyelids. This tape is an acrylic-based medical adhesive and is commonly used to keep eyelids closed during general anesthesia. MARSIs can largely be prevented through evidence-based clinical guidance. Enhancing awareness of MARSIs among anesthesia providers and perianesthesia nurses is crucial to prevent and manage such injuries effectively.

[Changes in fingerprint and chromaticity values of Mori Cortex during stir-frying process].

This study aims to reveal the dynamics of the HPLC fingerprint, chromaticity values, and main chemical components of Mori Cortex during the stir-frying process. The fingerprints of raw and processed products of Mori Cortex were established. The content of mulberroside A, oxyresveratrol, kuwanon G, and kuwanon H in the samples and the chromaticity values of the samples were determined. Furthermore, the similarity evaluation of fingerprints and the correlation analysis between fingerprints and chromaticity values were carried out. The results showed that the fingerprints of raw and processed products of Mori Cortex had high similarity, and the overall changes in the content of the main chemical components in the stir-frying process were similar. According to the experience, when the stir-frying is moderate, the total chromaticity value difference |ΔE~*_(ab)| is above 1.5. With the extension of stir-frying time, the L~* and E~*_(ab) values keep decreasing, and the a~* value keeps increasing. The results of the correlation analysis between fingerprints and chromaticity values showed that peaks 1(5-hydroxy maltol), 2(mulberroside A), 3, 4, 6, 7, 11(oxyresveratrol), 14, 17(kuwanon G), and 18(kuwanon H) had significant correlations with the chromaticity values. Quantitative analysis of the four components with higher content showed that the content of the four components decreased to varying degrees when the stir-frying was excessive. In addition, 5-hydroxy maltol was produced after stir-frying of Mori Cortex, and the fingerprint and chromaticity values showed regular changes during the stir-frying process. The chromaticity can be included in the evaluation of the stir-frying process of Mori Cortex, which provides a reference for standardizing the quality of stir-fried Mori Cortex.

Genome-wide CRISPR screening reveals genes essential for cell viability and resistance to abiotic and biotic stresses in Bombyx mori.

High-throughput genetic screens are powerful methods to interrogate gene function on a genome-wide scale and identify genes responsible to certain stresses. Here, we developed a piggyBac strategy to deliver pooled sgRNA libraries stably into cell lines. We used this strategy to conduct a screen based on genome-wide clustered regularly interspaced short palindromic repeat technology (CRISPR)-Cas9 in Bombyx mori cells. We first constructed a single guide RNA (sgRNA) library containing 94,000 sgRNAs, which targeted 16,571 protein-coding genes. We then generated knockout collections in BmE cells using the piggyBac transposon. We identified 1006 genes that are essential for cell viability under normal growth conditions. Of the identified genes, 82.4% (829 genes) were homologous to essential genes in seven animal species. We also identified 838 genes whose loss facilitated cell growth. Next, we performed context-specific positive screens for resistance to biotic or nonbiotic stresses using temperature and baculovirus separately, which identified several key genes and pathways from each screen. Collectively, our results provide a novel and versatile platform for functional annotations of B. mori genomes and deciphering key genes responsible for various conditions. This study also shows the effectiveness, practicality, and convenience of genome-wide CRISPR screens in nonmodel organisms.

Large-scale pathway reconstruction and colorimetric screening accelerate cellular metabolism engineering.

The capability to manipulate and analyze hard-wired metabolic pathways sets the pace at which we can engineer cellular metabolism. Here, we present a framework to extensively rewrite the central metabolic pathway for malonyl-CoA biosynthesis in yeast and readily assess malonyl-CoA output based on pathway-scale DNA reconstruction in combination with colorimetric screening (Pracs). We applied Pracs to generate and test millions of enzyme variants by introducing genetic mutations into the whole set of genes encoding the malonyl-CoA biosynthetic pathway and identified hundreds of beneficial enzyme mutants with increased malonyl-CoA output. Furthermore, the synthetic pathways reconstructed by randomly integrating these beneficial enzyme variants generated vast phenotypic diversity, with some displaying higher production of malonyl-CoA as well as other metabolites, such as carotenoids and betaxanthin, thus demonstrating the generic utility of Pracs to efficiently orchestrate central metabolism to optimize the production of different chemicals in various metabolic pathways. Pracs will be broadly useful to advance our ability to understand and engineer cellular metabolism.

Effect of Repetitive Transcranial Magnetic Stimulation on Post-stroke Dysphagia in Acute Stage.

Repetitive transcranial magnetic stimulation (rTMS) play a important role for rehabilitation in stroke. But therapeutic schedule of rTMS in dysphagia after acute stroke is still controversial. The purpose of this study was to investigate the therapeutic effect of rTMS with different frequencies on dysphagia after acute stroke. From August 2019 to December 2020, 45 patients with post-stroke dysphagia were selected as research subjects, and randomly divided into 3 groups: the high frequency stimulation on bilateral hemisphere group (High group), bilateral high frequency stimulation on the affected hemisphere and low frequency stimulation on the unaffected hemisphere group (High-low group), and sham stimulation group (Sham group). On the basis of routine swallowing training (30 min) for all patients, the high group received 5 Hz rTMS in both hemispheres, the high- low group received 5 Hz rTMS in the unaffected hemisphere, 1 Hz rTMS in the affected hemisphere, and the sham stimulation group received sham stimulation in bilateral hemisphere. All participants were assessed with dysphagia handicap index (DHI), functional oral intake scale (FOIS) and videofluoroscopic swallowing study (VFSS) before the intervention (T1), immediately after intervention (T2) and 1 month after the intervention (T3). Meanwhile, according to the results of VFSS, Rosenbek penetration aspiration scale (PAS), the moving distance of hyoid bone towards the superior side (H), and pharyngeal response time (T) were analyzed and evaluated. After intervention, all three groups showed significant improvement in post-treatment scores from baseline (P = 0.000). The results of DHI, PAS and H showed that the improvement in high group and high-low group was significantly greater than sham group (P = 0.000). The results of FOIS and T showed that the improvement of bilateral high-frequency group was significantly greater than that of high-low group and sham group (P = 0.000), and the difference lasted until 1 month after the end of treatment. Therefore, bilateral pharyngeal cortex high frequency rTMS and affected side high frequency/unaffected side low frequency rTMS can effectively improve swallowing disorder after acute stroke. However, the effect of bilateral high frequency rTMS is significantly higher than high-low in improving oral feeding function and pharyngeal response time.

A water pricing model for urban areas based on water accessibility.

Water resource, with properties of scarcity, is one of the vital resource endowments. Like land resources, the prices of these resource endowments should be correlated to their locations to follow fair and reasonable principles. The current water price systems are mainly policy-oriented fixed regimes. And the water use was charged according to the regional-average situation with scarce consideration of the fine-scale geographical water accessibility. With a combination of the water accessibility and the current water pricing regime, this paper first proposed a novel water pricing model, the Water Price at Grid-scale (WPG) model, to dynamically allocate water prices to fine grids for urban residents. The WPG model was examined in the case study of the Han River Basin in the Hubei province of China. The specific results were: (1) the Pgrid of Tier I is between 0.66 and 3.94 yuan/m³, the Pgrid of Tier II is between 0.57 and 5.44 yuan/m³, and the Pgrid of Tier III is between 0.47 and 6.94 yuan/m³ in the study area. (2) the grids with more water acquisition generally have lower water prices than others and vice versa. (3) the average water prices in tiers obtained by the WPG model are generally higher than that derived from the current water pricing system. The results proved that the proposed WPG model spatially allocates the three-tier water prices into grids of urban areas. The WPG framework can be adopted in any society by involving its water price regimes and adjusting the scale of grids and the pricing year. This study provided a new viewpoint of domestic water pricing involving fine-scale water accessibility. The WPG model has great potential to ease water shortage pressure in water-limited societies and can be utilized and loaded into the current smart-city network for efficient and fine-scale water resource management.

[Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species].

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 µL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Sperm-derived RNAs improve the efficiency of somatic cell nuclear transfer (SCNT) through promoting R-loop formation.

Mammalian sperm and oocytes are haploid cells that carry parental genetic and epigenetic information for their progeny. The cytoplasm of oocytes is also capable of reprograming somatic cells to establish totipotency through somatic cell nuclear transfer (SCNT). However, epigenetic barriers seriously counteract SCNT reprogramming. Here, we found that sperm-derived RNAs elevated chromatin accessibility of nuclear donor cells concurrent with the appearance of increased RNA amount and decreased cell proliferation, instead of activating DNA damage response. Additionally, tri-methylation of lysine 9 on histone H3 (H3K9me3) and the H3K9 methyltransferase SUV39H2 were significantly downregulated by the sperm-derived RNA treatment. Our findings thus raise a fascinating possibility that sperm RNA-induced R-loops may activate gene expression and chromatin structure, thereby promoting SCNT reprogramming.

First report of Colletotrichum circinans causing anthracnose on Polygonatum sibiricum in Liaoning Province, China.

Polygonatum sibiricum (Huangjing, Siberian Solomon's seal) is a perennial plant of the family Asparagaceae. Used in traditional Chinese medicine in northeast China, P. sibiricum has become widely cultivated in recent years. During late June and early July 2021, leaf fleck symptoms were observed on P. sibiricum at a plantation in Liaoning Province, a major Huangjing production region in China. According to our survey, the incidence of the disease was over 50%. Symptoms initially appeared on infected leaves as necrotic spots, which increased in size and extended to circular or elliptical, pale to light brown lesions with well-defined dark brown margin. To identify the pathogen, leaves showing typical symptoms of infected plants were collected. Leaf samples were excised from the junction of both healthy and symptomatic tissues as 5 mm diameter pieces. Tissue samples were surface-sterilized with successive washes of 75% ethanol (25 sec), 0.1% mercuric chloride solution (1.5 min), three rinses with sterile distilled water, and then left to air dry (Zhongda 2007). Finally, the tissue pieces were plated on potato dextrose agar (PDA), and incubated at 25°C for 5 days in the dark. Six individual colonies with similar cultural morphology were isolated by transferring mycelium plugs from the margins of colonies to new PDA dishes and were incubated under the same conditions. Two representative isolates (S3-2, S5-3) were used for morphological and molecular identifications. Colonies on PDA were initially whitish, then turned dark grey with age, and were covered with aerial mycelium. On the reverse side, colonies were initially whitish and turned grey to dark black with age. Conidia were hyaline, aseptate, little curved and apex acute, and with sizes of 17.5 to 22.5×3 to 4 µm. Setae were dark brown, subuliform with 2 to 4 septate, 110 to 160 µm long. The morphological and cultural characteristics are consistent with the description of Colletotrichum circinans (Damm, et al. 2009). For molecular identification, genomic DNA was extracted from mycelia of the representative fungal strains. Internal transcribed spacers (ITS) region, actin (ACT), chitin synthase 1(CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and betatubulin (TUB2) genes amplified by using specific primers and PCR conditions described in (Ji Ma, et al. 2020). The resulting sequences were submitted to the GenBank. BlastN revealed that ITS(OM019299, OM937757), ACT(OM455393, OM937756), CHS1(OM455391, OM937754), GAPDH(OM455392, OM937755), Tub2(OM455394, OM937758) were identified as C. circinans. The ITS, ACT, CHS1, GAPDH, Tub2 sequences of the strains and other Colletotrichum species were multiple aligned using ClustalW implemented in MEGA5.1 and used for phylogenetic tree construction by Maximum likelihood method, with bootstrap value of 1000 replicates (Tamura et al. 2011). Monilochaetes infuscans (CBS:869.96) was used as an outgroup. The analysis indicated that the strains grouped with C. circinans with good bootstrap support, further supporting the morphological and single-gene molecular identifications. Pathogenicity was demonstrated by in vivo inoculation of leaves of three-month-old healthy P. sibiricum seedlings. Before inoculation, all the leaves of P. sibiricum were surface-sterilized with 75% ethanol and washed with sterile water twice (Jin Chen, et al. 2021). Each plant was inoculated by placing three mycelial plugs (5mm; taken from an actively-growing colony of the isolates) on a single healthy leaf, and the second leaf of each plant was inoculated by a sterile PDA plug as a control. After inoculation, plants were placed in an incubator held at a constant 25℃ and relative humidity (>80%) with a 16h/8h day/night cycle. The experiment was repeated three times. The brown spots were observed after 6 days on inoculated leaves, while no visible disease symptoms were observed on control leaves. The acervulus and conidia were visible on the dorsal of diseased leaves 11-13 days after inoculation. The same pathogen was reisolated and confirmed as C.circinans by morphological comparison, fulfilling Koch's postulates. These results illustrated that C.circinans was responsible for the anthracnose disease of P. sibiricum. To our knowledge, this is the first report of C. circinans causing anthracnose on P. sibiricum in Liaoning Province, and an effective control method should be adopted to reduce losses.

Research on Processing-Induced Chemical Variations in Polygonatum Cyrtonema Rhizome by Integrating Metabolomics and Glycomics.

Polygonatum cyrtonema rhizome (PCR), the dried sweet rhizome of Polygonatum cyrtonema Hua, is commonly used as a tonic remedy and a functional food in Asia, Europe, and North America. Multiple components, including secondary metabolites, monosaccharides, oligosaccharides, and polysaccharides, collectively contribute to the therapeutic effects of PCR. Processing time exerts a significant influence on the quality of PCR, but the various processing stages have not been comprehensively chemically profiled. It is urgent to study processing-induced chemical variations in PCR to control the processing degree. In this study, multiple chromatographic and mass spectrometric techniques were used in combination with multivariate statistical analysis to perform qualitative and quantitative research on secondary metabolites and carbohydrates in PCR during processing. The results demonstrated that PCR processing can be divided into three stages, namely the raw stage (0 h), the middle stage (1-6 h), and the late stage (8-18 h). Twenty differential compounds were screened from secondary metabolites and oligosaccharides to distinguish PCR in different processing stages. Furthermore, the chemical variations of Polygonatum cyrtonema polysaccharides (PCP) also entered a new stage after processing for 6 h. Multiple chemical mechanisms, including hydrolysis, oxidative decomposition, dehydration, Maillard reaction, and polymerization were involved in the processing. This work provides a scientific basis to reveal the relationship between processing stage and chemical variations.

Creation of a Yeast Strain with Co-Translationally Acylated Nucleosomes.

Structurally diverse acylations have been identified as post-translational modifications (PTMs) on histone lysine residues, but their functions and regulations remain largely unknown. Interestingly, in nature, a lysine acylation analog, pyrrolysine, is introduced as a co-translational modification (CTM) through genetic encoding. To explore this alternative life form, we created a model organism Saccharomyces cerevisiae containing site-specific lysine CTMs (acetyl-lysine, crotonyl-lysine, or another synthetic analog) at histone H3K56 using non-canonical amino acid mutagenesis to afford a chemically modified nucleosome in lieu of their own in vivo. We further demonstrated that acetylation of histone H3K56 partly tends to provide a more favorable chromatin environment for DNA repair in yeast compared to crotonylation and crosstalk with other PTMs differently. This study provides a potentially universal approach to decipher the consequences of different histone lysine PTMs in eukaryotes.

Early cleavage of preimplantation embryos is regulated by tRNAGln-TTG-derived small RNAs present in mature spermatozoa.

tRNA-derived small RNAs (tsRNAs) from spermatozoa could act as acquired epigenetic factors and contribute to offspring phenotypes. However, the roles of specific tsRNAs in early embryo development remain to be elucidated. Here, using pigs as a research model, we probed the tsRNA dynamics during spermatogenesis and sperm maturation and demonstrated the delivery of tsRNAs from semen-derived exosomes to spermatozoa. By microinjection of antisense sequences into in vitro fertilized oocytes and subsequent single-cell RNA-seq of embryos, we identified a specific functional tsRNA group (termed here Gln-TTGs) that participate in the early cleavage of porcine preimplantation embryos, probably by regulating cell cycle-associated genes and retrotransposons. We conclude that specific tsRNAs present in mature spermatozoa play significant roles in preimplantation embryo development.

Quantifying Protein Electrostatic Interactions in Cells by Nuclear Magnetic Resonance Spectroscopy.

Most proteins perform their functions in cells. How the cellular environment modulates protein interactions is an important question. In this work, electrostatic interactions between protein charges were studied using in-cell nuclear magnetic resonance (NMR) spectroscopy. A total of eight charge pairs were introduced in protein GB3. Compared to the charge pair electrostatic interactions in a buffer, five charge pairs in cells displayed no apparent changes whereas three pairs had the interactions weakened by more than 70%. Further investigation suggests that the transfer free energy is responsible for the electrostatic interaction modulation. Both the transfer free energy of the folded state and that of the unfolded state can contribute to the cellular environmental effect on protein electrostatics, although the latter is generally larger (more negative) than the former. Our work highlights the importance of direct in-cell studies of protein interactions and thus protein function.

Multifunctional optoelectronic device based on graphene-coupled silicon photonic crystal cavities.

We present a hybrid device based on graphene-coupled silicon (Si) photonic crystal (PhC) cavities, featuring triple light detection, modulation, and switching. Through depositing single-layer graphene onto the PhC cavity, the light-graphene interaction can be enhanced greatly, which enables significant detection and modulation of the resonant wavelength. The device is designed to generate a photocurrent directly by the photovoltaic effect and has an external responsivity of ∼14 mA/W at 1530.8 nm (on resonance), which is about 10 times higher than that off-resonance. Based on the thermo-optical effect of silicon and graphene, the device is also demonstrated in electro-optical and all-optical modulation. Also, due to the high-quality (Q) factor of the resonate cavity, the device can implement low threshold optical bistable switching, and it promises a fast response speed, with a rise (fall) time of ∼0.4 µs (∼0.5 µs) in the all-optical switch and a rise (fall) time of ∼0.5 µs (∼0.5 µs) in the electro-optical hybrid switch. The multifunctional photodetector, modulator, and optical bistable switch are achieved in a single device, which greatly reduces the photonic overhead and provides potential applications for future integrated optoelectronics.

Human sperm tsRNA as potential biomarker and therapy target for male fertility.

Infertility caused by male factors is routinely diagnosed by assessing traditional semen parameters. Growing evidence has indicated that the tsRNAs carried in sperm act as epigenetic factors and potential biomarkers for the assessment of sperm quality. We recently demonstrated that tRNAGln-TTG derived small RNAs played notable roles in the first cleavage of a porcine embryo. However, the function of human sperm tRNAGln-TTG derived small RNAs as a diagnostic biomarker and its role in early embryo development remains unclear. In this study, we found that human sperm tRNAGln-TTG derived small RNAs were highly associated with sperm quality. By microinjecting the antisense sequence into human tripronuclear (3PN) zygotes followed by single-cell RNA-sequencing, we found that human sperm tRNAGln-TTG derived small RNAs participated in the development of a human embryo. Furthermore, Gln-TTGs might influence embryonic genome activation by modulating noncoding RNA processing. These findings demonstrated that human sperm tRNAGln-TTG derived small RNAs could be potential diagnostic biomarkers and could be used as a clinical target for male infertility.

Expanding the Structural Diversity of Protein Building Blocks with Noncanonical Amino Acids Biosynthesized from Aromatic Thiols.

Incorporation of structurally novel noncanonical amino acids (ncAAs) into proteins is valuable for both scientific and biomedical applications. To expand the structural diversity of available ncAAs and to reduce the burden of chemically synthesizing them, we have developed a general and simple biosynthetic method for genetically encoding novel ncAAs into recombinant proteins by feeding cells with economical commercially available or synthetically accessible aromatic thiols. We demonstrate that nearly 50 ncAAs with a diverse array of structures can be biosynthesized from these simple small-molecule precursors by hijacking the cysteine biosynthetic enzymes, and the resulting ncAAs can subsequently be incorporated into proteins via an expanded genetic code. Moreover, we demonstrate that bioorthogonal reactive groups such as aromatic azides and aromatic ketones can be incorporated into green fluorescent protein or a therapeutic antibody with high yields, allowing for subsequent chemical conjugation.