Deep Amplicon Sequencing Reveals Culture Selection of Mycobacterium Tuberculosis by Clinical Samples.

The commonly-used drug susceptibility testing (DST) relies on bacterial culture and faces shortcomings such as long turnaround time and clone/subclone selection. We developed a targeted deep amplification sequencing (DAS) method directly applied to clinical specimens. In this DAS panel, we examined 941 drug-resistant mutations associated with 20 anti-tuberculosis drugs with an initial amount of 4 pg DNA and reduced clinical testing time from 20 days to two days. A prospective study was conducted using 115 clinical specimens mainly with Xpert® Mycobacterium tuberculosis/rifampicin (Xpert MTB/RIF) assay positive to evaluate drug-resistant mutation detection. DAS was performed on culture-free specimens, while culture-dependent isolates were used for phenotypic DST, DAS, and whole-genome sequencing (WGS). For in silico molecular DST, our result based on DAS panel revealed the similar accuracy to three published reports based on WGS. For 82 isolates, application of DAS showed better sensitivity (93.03% vs. 92.16%), specificity (96.10% vs. 95.02%), and accuracy (91.33% vs. 90.62%) than Mykrobe software using WGS. Compared to culture-dependent WGS, culture-free DAS provides a full picture of sequence variation at population level, exhibiting in detail the gain-and-loss variants caused by bacterial culture. Our study performs a systematic verification of the advantages of DAS in clinical applications and comprehensively illustrates the discrepancy in Mycobacterium tuberculosis before and after culture.

Formation and reactivity of a unique M⋯C-H interaction stabilized by carborane cages.

Broadening carborane applications has consistently been the goal of chemists in this field. Herein, compared to alkyl or aryl groups, a carborane cage demonstrates an advantage in stabilizing a unique bonding interaction: M⋯C-H interaction. Experimental results and theoretical calculations have revealed the characteristic of this two-center, two-electron bonding interaction, in which the carbon atom in the arene ring provides two electrons to the metal center. The reduced aromaticity of the benzene moiety, long distance between the metal and carbon atom in arene, and the upfield shift of the signal of M⋯C-H in the nuclear magnetic resonance spectrum distinguished this interaction from metal⋯C π interaction and metal-C(H) σ bonds. Control experiments demonstrate the unique electronic effects of carborane in stabilizing the M⋯C-H bonding interaction in organometallic chemistry. Furthermore, the M⋯C-H interaction can convert into C-H bond metallization under acidic conditions or via treatment with t-butyl isocyanide. These findings deepen our understanding regarding the interactions between metal centers and carbon atoms and provide new opportunities for the use of carboranes.

Inhibiting perovskite decomposition by a creeper-inspired strategy enables efficient and stable perovskite solar cells.

The commercialization of perovskite solar cells is badly limited by stability, an issue determined mainly by perovskite. Herein, inspired by a natural creeper that can cover the walls through suckers, we adopt polyhexamethyleneguanidine hydrochloride as a molecular creeper on perovskite to inhibit its decomposition starting from the annealing process. The molecule possesses a long-line molecular structure where the guanidinium groups can serve as suckers that strongly anchor cations through multiple hydrogen bonds. These features make the molecular creeper can cover perovskite grains and inhibit perovskite decomposition by suppressing cations' escape. The resulting planar perovskite solar cells achieve an efficiency of 25.42% (certificated 25.36%). Moreover, the perovskite film and device exhibit enhanced stability even under harsh damp-heat conditions. The devices can maintain >96% of their initial efficiency after 1300 hours of operation under 1-sun illumination and 1000 hours of storage under 85% RH, respectively.

Development and Validation of a Clinic Machine Learning Classifier for the Prediction of Risk Stratifications of Prostate Cancer Bone Metastasis Progression to Castration Resistance.

Objective: To explore the predictive factors and predictive model construction for the progression of prostate cancer bone metastasis to castration resistance. Methods: Clinical data of 286 patients diagnosed with prostate cancer with bone metastasis, initially treated with endocrine therapy, and progressing to metastatic castration resistant prostate cancer (mCRPC) were collected. By comparing the differences in various factors between different groups with fast and slow occurrence of castration-resistant prostate cancer (CRPC). Kaplan-Meier survival analysis and COX multivariate risk proportional regression model were used to compare the differences in the time to progression to CRPC in different groups. The COX multivariate risk proportional regression model was used to evaluate the impact of candidate factors on the time to progression to CRPC and establish a predictive model. The accuracy of the model was then tested using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: The median time for 286 mCRPC patients to progress to CRPC was 17 (9.5-28.0) months. Multivariate analysis showed that the lowest value of PSA (PSA nadir), the time when PSA dropped to its lowest value (timePSA), and the number of BM, and LDH were independent risk factors for rapid progression to CRPC. Based on the four independent risk factors mentioned above, a prediction model was established, with the optimal prediction model being a random forest with area under curve (AUC) of 0.946[95% CI: 0.901-0.991] and 0.927[95% CI: 0.864-0.990] in the training and validation cohort, respectively. Conclusion: After endocrine therapy, the PSA nadir, timePSA, the number of BM, and LDH are the main risk factors for rapid progression to mCRPC in patients with prostate cancer bone metastases. Establishing a CRPC prediction model is helpful for early clinical intervention decision-making.

Effect of Bridging Manner on the Transport Behaviors of Dimethyldihydropyrene/Cyclophanediene Molecular Devices.

A molecule-electrode interface with different coupling strengths is one of the greatest challenges in fabricating reliable molecular switches. In this paper, the effects of bridging manner on the transport behaviors of a dimethyldihydropyrene/cyclophanediene (DHP/CPD) molecule connected to two graphene nanoribbon (GNR) electrodes have been investigated by using the non-equilibrium Green's function combined with density functional theory. The results show that both current values and ON/OFF ratios can be modulated to more than three orders of magnitude by changing bridging manner. Bias-dependent transmission spectra and molecule-projected self-consistent Hamiltonians are used to illustrate the conductance and switching feature. Furthermore, we demonstrate that the bridging manner modulates the electron transport by changing the energy level alignment between the molecule and the GNR electrodes. This work highlights the ability to achieve distinct conductance and switching performance in single-molecular junctions by varying bridging manners between DHP/CPD molecules and GNR electrodes, thus offering practical insights for designing molecular switches.

Harnessing synergistic effects in GQD@Pt(II) nanocomposites for enhanced photovoltaic performance: a computational study.

CONTEXT: The development of efficient solar energy conversion technologies is crucial for addressing global energy challenges and reducing reliance on fossil fuels. Platinum(II) complexes are promising materials for photovoltaic applications due to their strong light absorption and long-lived excited states. However, their narrow absorption in the visible spectrum and stability issues limit their performance. Combining platinum(II) complexes with graphene quantum dots (GQDs) can enhance photovoltaic performance by leveraging the complementary light harvesting and charge transfer characteristics of the two components. This study utilizes density functional theory (DFT) calculations to explore their electronic structures, charge transfer dynamics, and photoelectric performance. Specifically, it investigates the effects of incorporating different substituents, either electron-donating or electron-withdrawing, onto the fluorene motif of the Pt(II) complex. The findings reveal that combining GQDs with Pt(II) complexes extends light absorption into the UV range, enabling comprehensive solar utilization. Upon photoexcitation, electrons migrate between the GQD conduction band and the Pt(II) complex, stabilizing charges and enhancing extraction. Substituents significantly influence charge transfer dynamics: electron-withdrawing groups promote transfer to the GQD, while electron-donating groups encourage charge separation and delocalization. Nanocomposites featuring electron-donating substituents achieve the highest energy conversion efficiencies, with GQD@Pt(II)-NPh2 reaching 24.6%. This is attributed to improved light harvesting, efficient charge injection, and reduced recombination. These insights guide the rational design of GQD-Pt(II) nanocomposites, optimizing charge separation and transfer processes for enhanced photovoltaic performance. The computational approach employed here provides a robust tool for developing advanced materials in renewable energy technologies. METHODS: The computational studies reported in this work were performed using the DFT approach, specifically employing the hybrid functional PBE0. The PBE0 functional's accuracy in describing electronic structures and excited-state properties is essential for understanding charge transfer processes, photoabsorption, and emission characteristics in metal-organic complexes. Geometry optimizations and time-dependent DFT (TD-DFT) calculations were carried out to investigate the properties of the nanocomposites. The effects of solvents were replicated using the conductor-like polarizable continuum model (CPCM). The charge transfer length (ΔL) and interfragment charge transfer (ΔQ) were calculated using the Multiwfn software package, and all calculations were performed using the BDF software package.

Swallowing rehabilitation of patients undergoing T-tube implantation for the treatment of laryngotracheal stenosis.

OBJECTIVE: Patients with laryngotracheal stenosis (LTS) often have dysphagia after laryngotracheal reconstruction with T-tube insertion, which affects the quality of life. The purpose of this study is to observe the effect of swallowing rehabilitation therapy on the improvement of quality of life in patients of otolaryngology-head and neck surgery with dysphagia undergoing T-tube implantation treatment through longitudinal study. METHODS: Thirty-eight patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation were recruited. All patients received swallowing rehabilitation therapy. The assessment of swallowing function was performed using the 10-item Eating Assessment Tool (EAT-10), the 30 mL water swallow test (WST), and flexible endoscopic evaluation of swallow (FEES). RESULTS: After swallowing rehabilitation therapy, timing of swallowing, grade of dysphagia, performance on FEES and 30 mL WST, and EAT-10 score all improved. Thirty-eight patients successfully transitioned to oral feeding and were able to remove their nasogastric tubes without experiencing any complications, including aspiration pneumonia. CONCLUSION: For patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation, swallowing rehabilitation therapy could improve swallowing function of the patients, so as to reduce the potential harm caused by the pain and complications of surgery experienced by patients.

Quantification of gut microbiome metabolites using chemical isotope derivatization strategy combined with LC-MS/MS: Application in neonatal hypoxic-ischemic encephalopathy rat model.

The gut microbiome plays pivotal roles in various physiological and pathological processes, with key metabolites including short chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (TRP) derivatives gaining significant attention for their diverse physiological roles. However, quantifying these metabolites presents challenges due to structural similarity, low abundance, and inherent technical limitations in traditional detection methods. In this study, we developed a precise and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method utilizing a chemical isotope derivatization technique employing 4-(aminomethyl)-N,N-dimethylaniline-d0/d6 (4-AND-d0/d6) reagents to quantify 37 typical gut microbiome-derived metabolites. This method achieved an impressive 1500-fold enhancement in sensitivity for detecting metabolites, compared to methods using non-derivatized, intact molecules. Moreover, the quantitative accuracy of our chemical isotope derivatization strategy proved comparable to the stable isotope labeled internal standards (SIL-IS) method. Subsequently, we successfully applied this newly developed method to quantify target metabolites in plasma, brain, and fecal samples obtained from a neonatal hypoxic-ischemic encephalopathy (HIE) rat model. The aim was to identify crucial metabolites associated with the progression of HIE. Overall, our sensitive and reliable quantification method holds promise in elucidating the role of gut microbiome metabolites in the pathogenesis of various diseases.

Stabilizing Zinc Hexacyanoferrate Cathode by Low Contents of Cs Cations for Aqueous Zn-Ion Batteries.

Exploring cathode materials with excellent electrochemical performance is crucial for developing rechargeable aqueous zinc ion batteries (RAZIBs). Zinc hexacyanoferrate (ZnHCF), a promising candidate of cathode materials for RAZIBs, suffers from severe electrochemical instability issues. This work reports using low contents of alkaline metal cations as electrolyte additives to improve the cycle performance of ZnHCF. The cations with large sizes, particularly Cs+, changes the intercalation chemistry of ZnHCF in RAZIBs. During cycling, Cs+ cations co-inserted into ZnHCF stabilize the host structure. Meanwhile, a stable phase of CsZn[Fe(CN)6] forms on the ZnHCF cathode, suppressing the loss of active materials through dissolution. ZnHCF gradually converts to an electrochemically inert Zn-rich phase during long-term cycling in aqueous electrolyte, leading to irreversible capacity loss. Introducing Cs+ in the electrolyte inhibits this conversion reaction, resulting in the extended lifespan. Owing to these advantages, the capacity retention rate of ZnHCF/Zn full batteries increases from the original 7.0 % to a high value of 54.6 % in the electrolyte containing 0.03 M of Cs2SO4 after 300 cycles at 0.25 A ⋅ g-1. This research provides an in-depth understanding of the electrochemical behavior of ZnHCF in aqueous zinc electrolyte, beneficial for further optimizing ZnHCF and other metal hexacyanoferrates.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: A prospective cohort study.

BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. ERAS can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay (LOS) after surgery. RESULTS: A total of 245 patients (age of 79.8 ± 3.4 yr) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between non-frail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.

FPNC Net: A hydrogenation catalyst image recognition algorithm based on deep learning.

The identification research of hydrogenation catalyst information has always been one of the most important businesses in the chemical industry. In order to aid researchers in efficiently screening high-performance catalyst carriers and tackle the pressing challenge at hand, it is imperative to find a solution for the intelligent recognition of hydrogenation catalyst images. To address the issue of low recognition accuracy caused by adhesion and stacking of hydrogenation catalysts, An image recognition algorithm of hydrogenation catalyst based on FPNC Net was proposed in this paper. In the present study, Resnet50 backbone network was used to extract the features, and spatially-separable convolution kernel was used to extract the multi-scale features of catalyst fringe. In addition, to effectively segment the adhesive regions of stripes, FPN (Feature Pyramid Network) is added to the backbone network for deep and shallow feature fusion. Introducing an attention module to adaptively adjust weights can effectively highlight the target features of the catalyst. The experimental results showed that the FPNC Net model achieved an accuracy of 94.2% and an AP value improvement of 19.37% compared to the original CenterNet model. The improved model demonstrates a significant enhancement in detection accuracy, indicating a high capability for detecting hydrogenation catalyst targets.

Identification of CH2-linked quinolone-aminopyrimidine hybrids as potent anti-MRSA agents: Low resistance potential and lack of cross-resistance with fluoroquinolone antibiotics.

The structural optimization of B14, an antibacterial agent we previously obtained, has led to the discovery of a new class of CH2-linked quinolone-aminopyrimidine hybrids with potent anti-MRSA activities. Surprisingly, the hybrids lacking a C-6 fluoro atom at the quinolone nucleus showed equal or even stronger anti-MRSA activities than their corresponding 6-fluoro counterparts, despite the well-established structure-activity relationships (SARs) indicating that the 6-fluoro substituent enhances the antibacterial activity in conventional fluoroquinolone antibiotics. Moreover, these new hybrids, albeit structurally related to conventional fluoroquinolones, showed no cross-resistance with fluoroquinolone drugs. The most active compound, 15m, exhibited excellent activities with a MIC value of 0.39 µg/mL against both fluoroquinolone-sensitive strain USA500 and -resistant MRSA isolate Mu50. Further resistance development studies indicated MRSA is unlikely to acquire resistance against 15m. Moreover, 15m displayed favorable in vivo half-life and safety profiles. These findings suggest a rationale for further evolution of quinolone antibiotics with a high barrier to resistance.

S100 protein family: Emerging role and mechanism in digestive tract cancer (Review).

Digestive tract cancer is one of the most common types of cancers globally, with ~4.8 million new cases and 3.4 million cancer­associated deaths in 2018, accounting for 26% of cancer incidence and 35% of cancer­related deaths worldwide. S100 protein family is involved in regulating cancer cell proliferation, angiogenesis, epithelial­mesenchymal transition (EMT), metastasis, metabolism and immune microenvironment homeostasis. The critical role of S100 protein family in digestive tract cancer involves complicated mechanisms, such as cancer stemness remodeling, anaerobic glycolysis regulation, tumor­associated macrophage differentiation and EMT. The present study systematically reviewed published studies on the compositions, function and the underlying molecular mechanisms of the S100 family, as well as guidance for diagnosis, treatment and prognosis of digestive tract cancer. Systematic review of the roles and underlying molecular mechanisms of S100 protein family may provide new insight into exploring potential cancer biomarkers and the optimized therapeutic strategies for digestive tract cancer.

Rare-Earth Metalloligands for Low-Valent Cobalt Complexes: Fine Electronic Tuning via Co→RE Dative Interactions.

Rare-earth metalloligand supported low-valent cobalt complexes were synthesized by utilizing a small-sized heptadentate phosphinomethylamine LsNH3 and a large-sized arene-anchored hexadentate phosphinomethylamine LlArH3 ligand precursors. The RE(III)-Co(-I)-N2 (RE = Sc, Lu, Y, Gd, La) complexes containing rare-earth metals including the smallest Sc and largest La were characterized by multinuclear NMR spectroscopy, X-ray diffraction analysis, electrochemistry, and computational studies. The Co(-I)→RE(III) dative interactions were all polarized with major contributions from the 3dz2 orbital of the cobalt center, which was slightly affected by the identity of rare-earth metalloligands. The IR spectroscopic data and redox potentials obtained from cyclic voltammetry revealed that the electronic property of the Co(-I) center was finely tuned by the rare-earth metalloligand, which was revealed by variation of the ligand systems containing LsN, LmN, and LlAr. Unlike the direct alteration of the electronic property of metal center via an ancillary ligand, such a series of rare-earth metalloligand represents a smooth strategy to tune the electronic property of transition metals.

Minimizing Voltage Losses via Synergistically Reducing Hetero-Interface Energy Offset for High Efficiency Perovskite Solar Cells.

The open circuit voltage (VOC) losses at multiple interfaces within perovskite solar cells (PSCs) limit the improvements in power conversion efficiency (PCE). Herein, a tailored strategy is proposed to reduce the energy offset at both hetero-interfaces within PSCs to decrease the VOC losses. For the interface of perovskite and electron transport layer where exists a mass of defects, it uses the pyromellitic acid to serve as a molecular bridge, which reduces non-radiative recombination and energy level offset. For the interface of perovskite and hole transport layer, which includes a passivator of PEAI, the detrimental effect (negative shift of work function) of PEAI passivation and optimizing the interface energy level alignment are neutralized by incorporating (2-(4-(bis(4-methoxyphenyl)amino)phenyl)-1-cyanovinyl)phosphonic acid. Owing to synergistically reduced hetero-interface energy offset, the PSCs achieve a PCE of 25.13%, and the VOC is increased from 1.134 to 1.174 V. In addition, the resulting PSCs possess enhanced stability, the unencapsulated PSCs can maintain ≈96% and ≈97% of their initial PCE after 2000 h of aging under ambient conditions and 210 h under operation conditions.

Effects of building envelope features on airflow and pollutant dispersion within a symmetric street canyon.

Building envelope features (BEFs) have attracted more and more attention as they have a significant impact on flow structure and pollutant dispersion within street canyons. This paper conducted CFD numerical models validated by wind-tunnel experiments, to explore the effects of the BEFs on characteristics of the airflow and pollutant distribution inside a symmetric street canyon under perpendicular incoming flow. Three different BEFs (balconies, overhangs, and wing walls) and their locations and continuity/discontinuity structures were considered. For each canyon with various BEFs, the air exchange rate (ACH), airflow patterns, and pollutant distributions were evaluated and compared in detail. The results show that compared to the regular canyon, the BEFs will reduce the ACH of the canyon, but increase the disturbances (the proportion of ACH') inside the canyon. The BEFs on the leeward wall have the least influence on the in-canyon airflow and pollutant distributions, followed by that on the windward wall. Then when the BEFs are on both walls, the ventilation capacity of the canyon is weakened greatly, and the pollutant concentration in the ground center is increased significantly, especially near the windward side. Moreover, the discontinuity BEFs will weaken the effect of the continuity BEFs on the in-canyon flow and dispersion, specifically, the discontinuity BEFs reduced the region of high pollutant concentration distributions. These findings can help optimize the BEFs design to enhance ventilation and mitigate traffic pollution.

Cascade Reaction in Organic Hole Transport Layer Enables Efficient Perovskite Solar Cells.

The doped organic hole transport layer (HTL) is crucial for achieving high-efficiency perovskite solar cells (PSCs). However, the traditional doping strategy undergoes a time-consuming and environment-dependent oxidation process, which hinders the technology upgrades and commercialization of PSCs. Here, we reported a new strategy by introducing a cascade reaction in traditional doped Spiro-OMeTAD, which can simultaneously achieve rapid oxidation and overcome the erosion of perovskite by 4-tert-butylpyridine (tBP) in organic HTL. The ideal dopant iodobenzene diacetate was utilized as the initiator that can react with Spiro to generate Spiro⋅+ radicals quickly and efficiently without the participation of ambient air, with the byproduct of iodobenzene (DB). Then, the DB can coordinate with tBP through a halogen bond to form a tBP-DB complex, minimizing the sustained erosion from tBP to perovskite. Based on the above cascade reaction, the resulting Spiro-based PSCs have a champion PCE of 25.76 % (certificated of 25.38 %). This new oxidation process of HTL is less environment-dependent and produces PSCs with higher reproducibility. Moreover, the PTAA-based PSCs obtain a PCE of 23.76 %, demonstrating the excellent applicability of this doping strategy on organic HTL.

Simulation study on functional group-modified Ni-MOF-74 for CH4/N2 adsorption separation.

This study employs grand canonical Monte Carlo (GCMC) simulations to investigate the impact of functional group modifications (CH3, OH, NH2, and OLi) on the adsorption performance of CH4/N2 on Ni-MOF-74. The results revealed that functional group modifications significantly increased the adsorption capacity of Ni-MOF-74 for both CH4 and N2. The packed methyl groups in CH3-Ni-MOF-74 create an environment conducive to CH4, leading to the highest CH4 adsorption capacity. The electrostatic potential distribution indicates that the strong electron-donating effect introduced by the alkali metal Li results in the highest electrostatic potential gradient in Li-O-Ni-MOF-74, leading to the strongest adsorption of N2, this is unfavorable for CH4/N2 separation. At 1500 kPa the selectivity order of adsorbents for mixed gases was as follows: CH3-Ni-MOF-74 > NH2-Ni-MOF-74 > OH-Ni-MOF-74 > Ni-MOF-74 > Li-O-Ni-MOF-74. This study highlights that CH3-Ni-MOF-74 possesses optimal CH4 selectivity and adsorption performance. Given the current lack of research on functionalized MOF-74 for the separation of CH4 and N2, the findings of this study will serve as a theoretical guide and provide references for the applications of CH4 adsorption and CH4/N2 separation.

A scandium metalloligand supported Ni(0) complex with a heterobimetallocycle: versatile reactivity with unsaturated bonds.

A N2-bridged tetranuclear Sc(III)-Ni(0) complex featuring a Ni → Sc interaction and a 4-membered [Sc-N-C-Ni] ring was synthesized and characterized. Bimetallic reactivity was demonstrated via reactions with a series of unsaturated compounds containing NC, CN, CC, CO and NN bonds.