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Summary: Earthquakes occur thousands of times every day around the world. They are naturally destructive seismic events and often result in soil liquefaction. Soil microbiota plays a vital role in soil environments and may serve as an effective indicator to assess soil liquefaction after earthquakes. This study aimed to detect the microbial community abundance and composition in soil samples of different depths. Soil samples were collected in Southern Taiwan immediately after the 2010 earthquake. Their physical characteristics were determined, and their microbial communities were analyzed through 16S amplicon sequencing. The results revealed that Nitrospirae phylum dominated in the liquefied layer. In particular, the genus HB118, dominant in the liquefied layer, was not detected at other soil depths or in the expelled liquefied soil. This finding not only provides valuable insights into changes in microbial community composition at different soil depths after earthquakes but also suggests a useful indicator for monitoring liquefied soil.

Photodetectors are widely applied in modern industrial fields because they convert light energy into electrical signals. We propose a printable silver (Ag) paste electrode for a highly flexible metal–semiconductor–metal (MSM) broadband visible light photodetector as a wearable and portable device. Single-crystal and surface-textured silicon substrates with thicknesses of 37.21 μm were fabricated using a wet etching process. Surface texturization on flexible Si substrates enhances the light-trapping effect and minimizes reflectance from the incident light, and the average reflectance is reduced by 16.3% with pyramid-like structures. In this study, semitransparent, conductive Ag paste electrodes were manufactured using a screen-printing with liquid-phase process to form a flexible MSM broadband visible light photodetector. The transmittance of the homemade Ag paste solution fell between 34.83% and 36.98% in the wavelength range of visible light, from 400 nm to 800 nm. The highest visible light photosensitivity was 1.75 × 104 at 19.5 W/m2. The photocurrents of the flexible MSM broadband visible light photodetector were slightly changed under concave and convex conditions, displaying stable and durable bending properties.

Abstract Background RNA secondary structural alignment serves as a foundational procedure in identifying conserved structural motifs among RNA sequences, crucially advancing our understanding of novel RNAs via comparative genomic analysis. While various computational strategies for RNA structural alignment exist, they often come with high computational complexity. Specifically, when addressing a set of RNAs with unknown structures, the task of simultaneously predicting their consensus secondary structure and determining the optimal sequence alignment requires an overwhelming computational effort of $$O(L^6)$$ O ( L 6 ) for each RNA pair. Such an extremely high computational complexity makes these methods impractical for large-scale analysis despite their accurate alignment capabilities. Results In this paper, we introduce REDalign, an innovative approach based on deep learning for RNA secondary structural alignment. By utilizing a residual encoder-decoder network, REDalign can efficiently capture consensus structures and optimize structural alignments. In this learning model, the encoder network leverages a hierarchical pyramid to assimilate high-level structural features. Concurrently, the decoder network, enhanced with residual skip connections, integrates multi-level encoded features to learn detailed feature hierarchies with fewer parameter sets. REDalign significantly reduces computational complexity compared to Sankoff-style algorithms and effectively handles non-nested structures, including pseudoknots, which are challenging for traditional alignment methods. Extensive evaluations demonstrate that REDalign provides superior accuracy and substantial computational efficiency. Conclusion REDalign presents a significant advancement in RNA secondary structural alignment, balancing high alignment accuracy with lower computational demands. Its ability to handle complex RNA structures, including pseudoknots, makes it an effective tool for large-scale RNA analysis, with potential implications for accelerating discoveries in RNA research and comparative genomics.

Abstract The inversion of substrate size specificity is an evolutionary roadblock for proteins. The Duf4243 dioxygenases GedK and BTG13 are known to catalyze the aromatic cleavage of bulky tricyclic hydroquinone. In this study, we discover a Duf4243 dioxygenase PaD that favors small monocyclic hydroquinones from the penicillic-acid biosynthetic pathway. Sequence alignments between PaD and GedK and BTG13 suggest PaD has three additional motifs, namely motifs 1-3, distributed at different positions in the protein sequence. X-ray crystal structures of PaD with the substrate at high resolution show motifs 1-3 determine three loops (loops 1-3). Most intriguing, loops 1-3 stack together at the top of the pocket, creating a lid-like tertiary structure with a narrow channel and a clearly constricted opening. This drastically changes the substrate specificity by determining the entry and binding of much smaller substrates. Further genome mining suggests Duf4243 dioxygenases with motifs 1-3 belong to an evolutionary branch that is extensively involved in the biosynthesis of natural products and has the ability to degrade diverse monocyclic hydroquinone pollutants. This study showcases how natural enzymes alter the substrate specificity fundamentally by incorporating new small motifs, with a fixed overall scaffold-architecture. It will also offer a theoretical foundation for the engineering of substrate specificity in enzymes and act as a guide for the identification of aromatic dioxygenases with distinct substrate specificities.

Abstract Aims The PIONEER‐HF and PARAGLIDE‐HF trials aimed to determine the efficacy and safety of the in‐hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real‐world routine care is unclear. This study aimed to investigate the applicability of the PIONEER‐HF and PARAGLIDE‐HF trials to real‐world AHF patients. Methods and results We identified 28 293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER‐HF eligible (n = 3683) and non‐eligible (n = 3502) patients with an LVEF ≤40%, and PARAGLIDE‐HF eligible (n = 5191) and non‐eligible (n = 5832) patients with an LVEF >40%. Over a mean follow‐up of 3.5 years, the PIONEER‐HF non‐eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88–1.04). No significant difference was found in the composite outcome between PARAGLIDE‐HF non‐eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90–1.04). Conclusions Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril–valsartan. Yet, non‐eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril–valsartan benefits in non‐eligible AHF patients.

Background: Cardiac power output (CPO) predicts outcomes in advanced heart failure (HF) and cardiogenic shock, but its role in early HF stages is unclear. This study assessed the prognostic value of CPO in coronary artery disease patients with asymptomatic left ventricular systolic dysfunction (ALVSD) at stage B HF. Methods: We conducted a retrospective analysis of coronary artery disease patients who underwent coronary and pulmonary artery catheterization between 2006 and 2016. Stage B HF with ALVSD was defined as left ventricular ejection fraction

Poly (butylene adipate-co-terephthalate), PBAT, is one of the most popular plastics nowadays and is becoming a large burden to the environment when PBAT waste is accumulated. Biodegradation of PBAT is an environmentally friendly method to treat PBAT waste. In the past two decades, a couple of microbial strains or mixed strains have been chemically characterized. From this, many PBAT depolymerases have been isolated and further structurally determined. The review we focused on the PBAT depolymerases that have been structurally characterized, including lipases, esterases, and cutinases. We also discussed which shape of the substrate-binding tunnels is beneficial for recognizing and decomposing polymer chains of PBAT, which would be important guidance in directing the designation of PBAT depolymerases.

Endocrine therapy that blocks estrogen receptor signaling has been effective for decades as a primary treatment choice for breast cancer patients expressing the estrogen receptor. However, the issue of drug resistance poses a significant clinical challenge. It is therefore critically important to create new therapeutic agents that can suppress ERα activity, particularly in cases of ESR1 mutations. This review highlights recent efforts in drug development of next generation ER-targeted agents, including oral selective ER degraders, proteolysis-targeting chimera ER degraders, and other innovative molecules, such as complete estrogen receptor antagonists and selective estrogen receptor covalent antagonists. The drug design, efficacy, and clinical trials for each compound are detailed herein.

Electrolyte balance is essential for the proper functioning of the body, and imbalances can lead to various health issues, some of which may be life-threatening. Therefore, measuring electrolyte concentrations is becoming increasingly important, particularly for athletes engaged in high-intensity and prolonged physical activity. In this project, we developed a highly sensitive sensing device capable of accurately and rapidly measuring electrolyte concentrations in mixed solutions, providing precise analysis of trace electrolyte levels. The sensor device requires no complex operational procedures and can quickly complete measurements, making it well-suited for point-of-care applications. Integration of regression models further enhances the device’s ability to estimate concentrations in mixed electrolyte solutions. The test results demonstrate that the device can detect subtle concentration variations, with a precision as low as 0.5 mM. This proposed sensing device offers a cost-effective and efficient solution for real-time monitoring of electrolyte levels in healthcare.

Semiconducting single‐walled carbon nanotubes (s‐SWNTs) have arisen a growing interest in field‐effect transistors (FETs) due to their advantages, such as lower fabrication temperature, flexibility, and solution processing applicability, compared to traditional silicon‐based FETs. In this study, diversifying the functionality of s‐SWNT‐based FETs is focused on, particularly emphasizing their use in nonvolatile photomemory applications. By selectively wrapping s‐SWNT with n‐type conjugated polymers (CPs), electron‐trapping and photoresponsive capabilities are endowed in the device. After optimizing the structure and aggregating behavior of n‐type CPs, a favorable supramolecular network comprising s‐SWNT and CPs is formed and applied in phototransistor memory. Accordingly, the device exhibits a high memory ratio and window of 105 and 75.7 V, representing its remarkable charge‐storage capabilities. In addition, the device demonstrates decent long‐term stability over 104 s and multilevel memory behavior driven by the varied gate bias or accumulated light‐gating periods. The proposed memory mechanism involves electrical writing and photoerasing processes with the existence of n‐type CPs on s‐SWNT, revealing the underlying principles of charge transfer between their heterojunction interfaces. Herein, this research contributes to developing advanced phototransistor memory, offering a promising avenue for future electronic applications.

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα+) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα+ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

Abstract The biosynthesis of neurotoxin aetokthonotoxin (AETX) that features a unique structure of pentabrominated biindole nitrile involves a first-of-its-kind nitrile synthase termed AetD, an enzyme that shares very low sequence identity to known structures and catalyzes an unprecedented mechanism. In this study, we resolve the crystal structure of AetD in complex with the substrate 5,7-di-Br-L-Trp. AetD adopts the heme oxygenase like fold and forms a hydrophobic cavity within a helical bundle to accommodate the indole moiety. A diiron cluster comprising two irons that serves as a catalytic center binds to the carboxyl O and the amino N of the substrate. Notably, we demonstrate that the AetD-catalyzed reaction is independent of the bromination of the substrate and also solved crystal structures of AetD in complex with 5-Br-L-Trp and L-Trp. Altogether, the present study reveals the substrate-binding pattern and validates the diiron cluster-comprising active center of AetD, which should provide important basis to support the mechanistic investigations into this class of nitrile synthase.

Abstract Using enzymes to hydrolyze and recycle poly(ethylene terephthalate) (PET) is an attractive eco-friendly approach to manage the ever-increasing PET wastes, while one major challenge to realize the commercial application of enzyme-based PET degradation is to establish large-scale production methods to produce PET hydrolytic enzyme. To achieve this goal, we exploited the industrial strain Pichia pastoris to express a PET hydrolytic enzyme from Caldimonas taiwanensis termed CtPL-DM. In contrast to the protein expressed in Escherichia coli, CtPL-DM expressed in P. pastoris is inactive in PET degradation. Structural analysis indicates that a putative N-glycosylation site N181 could restrain the conformational change of a substrate-binding Trp and hamper the enzyme action. We thus constructed N181A to remove the N-glycosylation and found that the PET hydrolytic activity of this variant was restored. The performance of N181A was further enhanced via molecular engineering. These results are of valuable in terms of PET hydrolytic enzyme production in industrial strains in the future. Graphical Abstract

Abstract Background As the RNA secondary structure is highly related to its stability and functions, the structure prediction is of great value to biological research. The traditional computational prediction for RNA secondary prediction is mainly based on the thermodynamic model with dynamic programming to find the optimal structure. However, the prediction performance based on the traditional approach is unsatisfactory for further research. Besides, the computational complexity of the structure prediction using dynamic programming is $$O(N^3)$$ O ( N 3 ) ; it becomes $$O(N^6)$$ O ( N 6 ) for RNA structure with pseudoknots, which is computationally impractical for large-scale analysis. Results In this paper, we propose REDfold, a novel deep learning-based method for RNA secondary prediction. REDfold utilizes an encoder-decoder network based on CNN to learn the short and long range dependencies among the RNA sequence, and the network is further integrated with symmetric skip connections to efficiently propagate activation information across layers. Moreover, the network output is post-processed with constrained optimization to yield favorable predictions even for RNAs with pseudoknots. Experimental results based on the ncRNA database demonstrate that REDfold achieves better performance in terms of efficiency and accuracy, outperforming the contemporary state-of-the-art methods.

Bio-degradation of poly(butylene adipate-co-terephthalate) is an attractive tactic but requires an effective hydrolytic enzyme. Here, the authors demonstrate that cutinases are highly potent PBAT-decomposing enzymes and their mechanism is proposed based on substrate-binding mode.

BackgroundThe optimal revascularization strategy for elderly patients with acute coronary syndrome (ACS) remains uncertain. We evaluated the impact of complete revascularization (CR) vs. incomplete revascularization (IR) in elderly ACS patients with multivessel disease (MVD) undergoing percutaneous coronary intervention (PCI).MethodsUsing registry data from 2011 to 2019, we conducted a propensity-score matched cohort study. Elderly patients (≥75 years) with ACS and MVD who underwent PCI were divided into CR and IR groups based on angiography during index hospitalization. Major adverse cardiovascular events (MACEs), including all-cause mortality, recurrent non-fatal myocardial infarction, and any revascularization, were assessed at 3-year follow-up.ResultsAmong 1,018 enrolled patients, 496 (48.7%) underwent CR and 522 (51.3%) received IR. After 1:1 propensity-score matching, we analyzed 395 pairs. At 3-year follow-up, CR was significantly associated with lower MACE risk compared to IR (16.7% vs. 25.6%, HR = 0.65, 95% CI: 0.47–0.88, p = 0.006), driven by reduced all-cause mortality. This benefit was consistent across all pre-specified subgroups, particularly in ST segment elevation (STE)-ACS patients. In non-STE (NSTE)-ACS subgroup analysis, CR was also associated with a lower risk of cardiac mortality compared to IR (HR = 0.30, 95% CI: 0.12–0.75, p = 0.01).ConclusionIn elderly ACS patients with MVD undergoing PCI, CR demonstrates superior long-term outcomes compared to IR, irrespective of STE- or NSTE-ACS presentation.

Abstract Background Asprosin is a novel fasting glucogenic adipokine discovered in 2016. Asprosin induces rapid glucose releases from the liver. However, its molecular mechanisms and function are still unclear. Adaptation of energy substrates from fatty acid to glucose is recently considered a novel therapeutic target in heart failure treatment. We hypothesized that the asprosin is able to modulate cardiac mitochondrial functions and has important prognostic implications in dilated cardiomyopathy (DCM) patients. Methods We prospectively enrolled 50 patients (86% male, mean age 55 ± 13 years) with DCM and followed their 5-year major adverse cardiovascular events from 2012 to 2017. Comparing with healthy individuals, DCM patients had higher asprosin levels (191.2 versus 79.7 ng/mL, P

In Taiwan, the incidence of non-ST segment elevation acute coronary syndrome (NSTE-ACS) continues to increase in recent years. The purpose of this guideline is to help health care professionals in Taiwan to use adequate tests and treatments for management of NSTE-ACS. For rapid diagnosis, in addition to history and physical examination, 0/3 h rapid diagnosis protocol with high sensitivity cardiac troponin assay is recommended in this guideline. Dual antiplatelet and anticoagulation therapies are important parts in the initial treatment. Risk stratification should be performed to identify high risk patients for early coronary angiography. Through evaluation of the coronary anatomy and other clinical factors, the decision for coronary revascularization, either by percutaneous coronary intervention or coronary artery bypass grafting, should be decided by the heart team. The duration of dual antiplatelet therapy should be given for at least 12 months after discharge. Other secondary preventive medications are also recommended for long term use. Keywords: Acute coronary syndrome, Guideline, Taiwan

Abstract Background Improving the hydrolytic performance of hemicellulases to degrade lignocellulosic biomass is of considerable importance for second-generation biorefinery. Xylanase, as the crucial hemicellulase, must be thermostable and have high activity for its potential use in the bioethanol industry. To obtain excellent xylanase candidates, it is necessary to understand the structure–function relationships to provide a meaningful reference to improve the enzyme properties. This study aimed to investigate the catalytic mechanism of a highly active hyperthermophilic xylanase variant, XYL10C-ΔN, for hemicellulose degradation. Results By removing the N-terminal 66 amino acids, the variant XYL10C-ΔN showed a 1.8-fold improvement in catalytic efficiency and could hydrolyze corn stover more efficiently in hydrolysis of corn stover; however, it retained similar thermostability to the wild-type XYL10C. Based on the crystal structures of XYL10C-ΔN and its complex with xylobiose, Glu175 located on loop 3 was found to be specific to GH10 xylanases and probably accounts for the excellent enzyme properties by interacting with Lys135 and Met137 on loop 2. Site-saturation mutagenesis confirmed that XYL10C-ΔN with glutamate acid at position 175 had the highest catalytic efficiency, specific activity, and the broadest pH-activity profile. The functional roles of Glu175 were also verified in the mutants of another two GH10 xylanases, XylE and XynE2, which showed increased catalytic efficiencies and wider pH-activity profiles. Conclusions XYL10C-ΔN, with excellent thermostability, high catalytic efficiency, and great lignocellulose-degrading capability, is a valuable candidate xylanase for the biofuel industry. The mechanism underlying improved activity of XYN10C-ΔN was thus investigated through structural analysis and functional verification, and Glu175 was identified to play the key role in the improved catalytic efficiency. This study revealed the importance of a key residue (Glu175) in XYN10C-ΔN and provides a reference to modify GH10 xylanases for improved catalytic performance.

Objective: This is an initial review of the safety and efficacy of anterior preperitoneal modified Kugel (MK) mesh herniorrhaphy application without using optional onlay mesh. Methods: We retrospectively reviewed patients who underwent herniorrhaphy by a single surgeon from July 1st, 2009 to December 31st, 2010. During these 18 months, a total of 72 patients underwent single-layer MK mesh herniorrhaphy. Anterior preperitoneal approach was used to place the mesh. If the patient's inguinal hernia defect did not exceed the memory ring of MK mesh, the onlay mesh was omitted. Postoperative results (wound infection, recurrence, and chronic pain/discomfort) were recorded and analyzed. Results: A total of 72 patients underwent anterior preperitoneal single layer MK mesh herniorrhaphy. One patient had recurrent hernia after 1 year and was treated with a laparoscopic transabdominal preperitoneal operation. The most common postoperative complaint was mild soreness which was self-resolving after 1 month. Mean total operative time (skin to skin) was 73 minutes. The average hospital stay was 2 days. Most of the postoperative complications including soreness (14%), pain for > 3 months (1.4%), and scrotal hematoma (1.4%) were self-resolving. One patient experienced wound infection, which was treated with oral antibiotics. One patient had recurrence 1 year after the operation. Conclusion: The postoperative complication and recurrence rates of single-layer MK mesh herniorrhaphy was comparable with previously reported tension-free repair. Single-layer application is safe and feasible. A longer follow-up period and larger study group with a control group are needed to verify our method.