Renal macrophages monitor and remove particles from urine to prevent tubule obstruction.

When the filtrate of the glomerulus flows through the renal tubular system, various microscopic sediment particles, including mineral crystals, are generated. Dislodging these particles is critical to ensuring the free flow of filtrate, whereas failure to remove them will result in kidney stone formation and obstruction. However, the underlying mechanism for the clearance is unclear. Here, using high-resolution microscopy, we found that the juxtatubular macrophages in the renal medulla constitutively formed transepithelial protrusions and "sampled" urine contents. They efficiently sequestered and phagocytosed intraluminal sediment particles and occasionally transmigrated to the tubule lumen to escort the excretion of urine particles. Mice with decreased renal macrophage numbers were prone to developing various intratubular sediments, including kidney stones. Mechanistically, the transepithelial behaviors of medulla macrophages required integrin ß1-mediated ligation to the tubular epithelium. These findings indicate that medulla macrophages sample urine content and remove intratubular particles to keep the tubular system unobstructed.

The Born in Guangzhou Cohort Study enables generational genetic discoveries.

Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health1. Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health.

The structure of the archaeal nuclease RecJ2 implicates its catalytic mechanism and inability to interact with GINS.

Bacterial RecJ exhibits 5'→3' exonuclease activity that is specific to ssDNA; however, archaeal RecJs show 5' or 3' exonuclease activity. The hyperthermophilic archaea Methanocaldococcus jannaschii encodes the 5'-exonuclease MjRecJ1 and the 3'-exonuclease MjRecJ2. In addition to nuclease activity, archaeal RecJ interacts with GINS, a structural subcomplex of the replicative DNA helicase complex. However, MjRecJ1 and MjRecJ2 do not interact with MjGINS. Here, we report the structural basis for the inability of the MjRecJ2 homologous dimer to interact with MjGINS and its efficient 3' hydrolysis polarity for short dinucleotides. Based on the crystal structure of MjRecJ2, we propose that the interaction surface of the MjRecJ2 dimer overlaps the potential interaction surface for MjGINS and blocks the formation of the MjRecJ2-GINS complex. Exposing the interaction surface of the MjRecJ2 dimer restores its interaction with MjGINS. The cocrystal structures of MjRecJ2 with substrate dideoxynucleotides or product dCMP/CMP show that MjRecJ2 has a short substrate binding patch, which is perpendicular to the longer patch of bacterial RecJ. Our results provide new insights into the function and diversification of archaeal RecJ/Cdc45 proteins.

BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma.

Interaction between programmed death-1 (PD-1) ligand 1 (PD-L1) on tumor cells and PD-1 on T cells allows tumor cells to evade T cell-mediated immune surveillance. Strategies targeting PD-1/PD-L1 have shown clinical benefits in a variety of cancers. However, limited response rates in hepatocellular carcinoma (HCC) have prompted us to investigate the molecular regulation of PD-L1. Here, we identify B cell lymphoma-2-associated transcription factor 1 (BCLAF1) as a key PD-L1 regulator in HCC. Specifically, BCLAF1 interacts with SPOP, an E3 ligase that mediates the ubiquitination and degradation of PD-L1, thereby competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Furthermore, we determined an SPOP-binding consensus (SBC) motif mediating the BCLAF1-SPOP interaction on BCLAF1 protein and mutation of BCLAF1-SBC motif disrupts the regulation of the SPOP-PD-L1 axis. In addition, BCLAF1 expression was positively correlated with PD-L1 expression and negatively correlated with biomarkers of T cell activation, including CD3 and CD8, as well as with the level of immune cell infiltration in HCC tissues. Besides, BCLAF1 depletion leads to a significant reduction of PD-L1 expression in vitro, and this reduction of PD-L1 promoted T cell-mediated cytotoxicity. Notably, overexpression of BCLAF1 sensitized tumor cells to checkpoint therapy in an in vitro HCC cells-Jurkat cells co-culture model, whereas BCLAF1-SBC mutant decreased tumor cell sensitivity to checkpoint therapy, suggesting that BCLAF1 and its SBC motif serve as a novel therapeutic target for enhancing anti-tumor immunity in HCC.

Unconventional Piezoelectricity of Two-Dimensional Materials Driven by the Hall Effect.

Piezoelectricity has been widely explored for nanoelectromechanical applications, yet its working modes are mainly limited in polar directions. Here we discover the intrinsic electro-mechanical response in crystal materials that is transverse to the conventional polarized direction, which is named unconventional piezoelectricity. A Hall-like mechanism is proposed to interpret unconventional piezoelectricity as charge polarization driven by a built-in electric field for systems with asymmetric Berry curvature distributions. Density functional theory simulations and statistical analyses justify such a mechanism and confirm that unconventional piezoelectricity is a general property for various two-dimensional materials with spin splitting or valley splitting. An empirical formula is derived to connect the conventional and unconventional piezoelectricity. The extended understanding of the piezoelectric tensor in quantum materials opens an opportunity for applications in multidirectional energy conversion, broadband operation, and multifunctional sensing.

Palladium/Platinum/Ruthenium Trimetallic Dendritic Nanozymes Exhibiting Enhanced Peroxidase-like Activity for Signal Amplification of Lateral Flow Immunoassays.

Developing ultrasensitive lateral flow immunoassays (LFIAs) has garnered significant attention in the field of point-of-care testing. In this study, a trimetallic dendritic nanozyme (Pd@Pt-Ru) was synthesized through Ru deposition on a Pd@Pt core and utilized to enhancing the sensitivity of LFIAs. Pd@Pt-Ru exhibited a Km value of 5.23 mM for detecting H2O2, which indicates an H2O2 affinity comparable with that of horseradish peroxidase. The Ru surface layer reduces the activation energy barrier, which increases the maximum reaction rate. As a proof of concept, the proposed Pd@Pt-Ru nanozyme was incorporated into LFIAs (A-Pd@Pt-Ru-LFIAs) for detecting human chorionic gonadotropin (hCG). Compared with conventional gold nanoparticle (AuNP)-LFIAs, A-Pd@Pt-Ru-LFIAs demonstrated 250-fold increased sensitivity, thereby enabling a visible detection limit as low as 0.1 IU/L. True positive and negative rates both reached 100%, which renders the proposed Pd@Pt-Ru nanozyme suitable for detecting hCG in clinical samples.

Controlled Sequential Doping of Metal Nanocluster.

Atomically precise doping of metal nanoclusters provides excellent opportunities not only for subtly tailoring their properties but also for in-depth understanding of composition (structure)-property correlation of metal nanoclusters and has attracted increasing interest partly due to its significance for fundamental research and practical applications. Although single and multiple metal atom doping of metal nanoclusters (NCs) has been achieved, sequential single-to-multiple metal atom doping is still a big challenge and has not yet been reported. Herein, by introducing a second ligand, a novel multistep synthesis method was developed, controlled sequential single-to-multiple metal atom doping was successfully achieved for the first time, and three doped NCs Au25Cd1(p-MBT)17(PPh3)2, Au18Cd2(p-MBT)14(PPh3)2, and [Au19Cd3(p-MBT)18]- (p-MBTH: para-methylbenzenethiol) were obtained, including two novel NCs that were precisely characterized via mass spectrometry, single-crystal X-ray crystallography, and so forth. Furthermore, sequential doping-induced evolutions in the atomic and crystallographic structures and optical and catalytic properties of NCs were revealed.

miR-485-3p targets SIRT1 in vascular smooth muscle cells mediating the occurrence of aortic dissection.

Studies have demonstrated a close correlation between MicroRNA and the occurrence of aortic dissection (AD). However, the molecular mechanisms underlying this relationship have not been fully elucidated and further exploration is still required. In this study, we found that miR-485-3p was significantly upregulated in human aortic dissection tissues. Meanwhile, we constructed in vitro AD models in HAVSMCs, HAECs and HAFs and found that the expression of miR-485-3p was increased only in HAVSMCs. Overexpression or knockdown of miR-485-3p in HAVSMCs could regulate the expression of inflammatory cytokines IL1ß, IL6, TNF-α, and NLRP3, as well as the expression of apoptosis-related proteins BAX/BCL2 and Cleaved caspase3/Caspase3. In the in vivo AD model, we have observed that miR-485-3p regulates vascular inflammation and apoptosis, thereby participating in the modulation of AD development in mice. Based on target gene prediction, we have validated that SIRT1 is a downstream target gene of miR-485-3p. Furthermore, by administering SIRT1 agonists and inhibitors to mice, we observed that the activation of SIRT1 alleviates vascular inflammation and apoptosis, subsequently reducing the incidence of AD. Additionally, functional reversal experiments revealed that overexpression of SIRT1 in HAVSMCs could reverse the cell inflammation and apoptosis mediated by miR-485-3p. Therefore, our research suggests that miR-485-3p can aggravate inflammation and apoptosis in vascular smooth muscle cells by suppressing the expression of SIRT1, thereby promoting the progression of aortic dissection.

High genetic diversity of the himalayan marmot relative to plague outbreaks in the Qinghai-Tibet Plateau, China.

Plague, as an ancient zoonotic disease caused by Yersinia pestis, has brought great disasters. The natural plague focus of Marmota himalayana in the Qinghai-Tibet Plateau is the largest, which has been constantly active and the leading source of human plague in China for decades. Understanding the population genetics of M. himalayana and relating that information to the biogeographic distribution of Yersinia pestis and plague outbreaks are greatly beneficial for the knowledge of plague spillover and arecrucial for pandemic prevention. In the present research, we assessed the population genetics of M. himalayana. We carried out a comparative study of plague outbreaks and the population genetics of M. himalayana on the Qinghai-Tibet Plateau. We found that M. himalayana populations are divided into two main clusters located in the south and north of the Qinghai-Tibet Plateau. Fourteen DFR genomovars of Y. pestis were found and exhibited a significant region-specific distribution. Additionally, the increased genetic diversity of plague hosts is positively associated with human plague outbreaks. This insight gained can improve our understanding of biodiversity for pathogen spillover and provide municipally directed targets for One Health surveillance development, which will be an informative next step toward increased monitoring of M. himalayana dynamics.

Genome assembly of redclaw crayfish (Cherax quadricarinatus) provides insights into its immune adaptation and hypoxia tolerance.

BACKGROUND: The introduction of non-native species is a primary driver of biodiversity loss in freshwater ecosystems. The redclaw crayfish (Cherax quadricarinatus) is a freshwater species that exhibits tolerance to hypoxic stresses, fluctuating temperatures, high ammonia concentration. These hardy physiological characteristics make C. quadricarinatus a popular aquaculture species and a potential invasive species that can negatively impact tropical and subtropical ecosystems. Investigating the genomic basis of environmental tolerances and immune adaptation in C. quadricarinatus will facilitate the development of management strategies of this potential invasive species. RESULTS: We constructed a chromosome-level genome of C. quadricarinatus by integrating Nanopore and PacBio techniques. Comparative genomic analysis suggested that transposable elements and tandem repeats drove genome size evolution in decapod crustaceans. The expansion of nine immune-related gene families contributed to the disease resistance of C. quadricarinatus. Three hypoxia-related genes (KDM3A, KDM5A, HMOX2) were identified as being subjected to positive selection in C. quadricarinatus. Additionally, in vivo analysis revealed that upregulating KDM5A was crucial for hypoxic response in C. quadricarinatus. Knockdown of KDM5A impaired hypoxia tolerance in this species. CONCLUSIONS: Our results provide the genomic basis for hypoxic tolerance and immune adaptation in C. quadricarinatus, facilitating the management of this potential invasive species. Additionally, in vivo analysis in C. quadricarinatus suggests that the role of KDM5A in the hypoxic response of animals is complex.

Tuning the Surface Stability and Li/Na Storage of MXenes by Controlling the Surface Termination Coverage.

2D transition metal carbides and/or nitrides, MXenes, are a class of widely studied materials with great potential for energy storage applications. The control of surface chemistry is an effective approach for preparing novel MXenes and modifying their electrochemical properties. However, an in-depth and systematic atomic-scale study of the effect of surface termination on MXene stability and electrochemical performance is scarce and thus is highly desired. Here, through high-throughput first-principles calculations, 28 stable chalcogen-functionalized M2CTz (M = V, Nb, and Ta, T = S, Se, and Te) under different chemical environments are identified. The reduction of termination coverage improves electrical conductivity but weakens in-plane stiffness. Intriguingly, based on charge transfer mechanism, the diffusion barrier of lithium/sodium atoms on the M2CTz exhibits a volcano-like relationship with termination coverage, and the ion diffusion channel formed in half termination coverage greatly accelerates lithium ion diffusion and returns to or exceeds sodium ion diffusion rate at full termination coverage. V2CSe2/Nb2CSz not only displays the large lithium/sodium capacity (592/409-466 mAhg-1) but also exhibits low barrier energy and open-circuit voltage, suggesting a promising candidate anode material for lithium/sodium-ion batteries. These findings provide insights into the design and fabrication of MXenes and tuning the electrochemical performance of MXenes by controlling termination coverage.

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

A distributed data processing scheme based on Hadoop for synchrotron radiation experiments.

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

Realization of double uniform line self-focusing of elliptical Airyprime beams.

Double line self-focusing characteristics of elliptical Airyprime beams (EAPBs) with different elliptical vertical-axis factor ß are investigated by varying the main ring radius r0. Overly large or small r0 results in the inhomogeneous distribution of light intensity at one linear focus of the double line self-focusing. Only when r0 is appropriate and ß is within a certain range, can double uniform line self-focusing happen to the EAPB. Moreover, the self-focusing ability of the second line self-focusing is weaken than that of the first line self-focusing. Under the premise of our selected values of beam parameters, the EAPB can achieve double uniform line self-focusing when r0 = 0.3 mm and ß = 0.58∼0.71. The focal length of the first line self-focusing, the lengths of double linear focus, and the self-focusing abilities of the double uniform line self-focusing can be regulated by varying ß within the range of 0.58∼0.71. If ß is smaller than 0.58 or larger than 0.71, it will lead to nonuniform line self-focusing. An explanation of the physical mechanism behind the double uniform line self-focusing of the EAPB is proposed. Finally, the experimental measurements of the line self-focusing of the EAPB confirm the validity of the above conclusions. This research provides a new solution on how to generate double uniform line self-focusing and new insights into the practical application of elliptical self-focusing beams.

Realization of a circularly transformed Airyprime beam with powerful autofocusing ability.

The reported autofocusing ability of a ring Airyprime beam array reaches up to 8632.40, while the strongest autofocusing ability of a circular Airyprime beam (CAPB) is only 1822.49. How can the autofocusing ability of a single beam reach the autofocusing ability of a beam array? To achieve this goal, a circularly transformed Airyprime beam (CTAPB) is introduced by following two steps. First, a circular equation transformation on the two transverse coordinates in the electric field expression of a propagating Airyprime beam is performed. Then, the electric field expression of a propagating Airyprime beam is integrated over the angle. The intensity profile of a CTAPB on the initial plane changes significantly with varying the primary ring radius r0. With increasing r0, therefore, the autofocusing ability of a CTAPB undergoes a process of first increasing and then decreasing, while the focal length always increases. A CTAPB exhibits more powerful autofocusing ability than a CAPB. The maximum autofocusing ability of a CTAPB can reach up to 8634.76, which is 4.74 times that of a CAPB, while the corresponding focal length is 95.11% of a CAPB. A CTAPB on the initial plane can be approximately characterized by a ring Airyprime beam array with sufficient number of Airyprime beams. Due to the better symmetry, a CTAPB has a slightly stronger autofocusing ability than a ring Airyprime beam array and almost the same focal length as a ring Airyprime beam array. The CTAPB is also experimentally generated, and the experimental results indicate that the CTAPB has powerful autofocusing ability. As a replacement of a CAPB and a ring Airyprime beam array, this introduced CTAPB can be applied to the scenes which involve abruptly autofocusing effect.

Outcomes of post-implantation syndrome after endovascular repair for Stanford type B aortic dissection.

OBJECTIVE: The aim of this study was to investigate the correlation between post-implantation syndrome (PIS) and long-term prognosis in patients with Stanford type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). METHODS: This retrospective study included 547 consecutive patients diagnosed with TBAD who underwent TEVAR at our institution between January 2014 and December 2019. Patients were categorized into two groups: the PIS group (patients with post-TEVAR PIS) and the non-PIS group (patients without post-TEVAR PIS). In-hospital and follow-up data were analyzed. RESULTS: The incidence of PIS was 28.9% (158/547 patients). No baseline differences were observed between the PIS (n = 158) and the non-PIS (n = 389) groups. The proportion of emergency surgery in the PIS group was higher than that in the non-PIS group (44.9% vs 26.0%; P < .001), the operation time was longer (median, 65.0; interquartile range [IQR], 56.0-75.0 minutes vs 56.0; IQR, 45.0-66.0 minutes; P < .001), the volume of contrast medium used (median, 65.0; IQR, 56.0-75.0 mL vs 56.0; IQR, 45.0-66.0 mL; P < .001), and the average number of trunk stents (1.85 ± 0.4 vs 1.34 ± 0.5 pieces; P < .001) and branch stents (0.7 ± 0.7 vs 0.2 ± 0.5 pieces; P < .001) used were more in the PIS group than in the non-PIS group. The incidence of supra-aortic branch procedures was higher in the PIS group than in the non-PIS group. There was no significant difference in device-related complications (DRCs) or 30-day mortality between the two groups (2.5% vs 4.4%; P = .442 and 1.3% vs 1.3%; P = .688, respectively). Univariate and multivariable logistic regression analysis showed that emergency surgery, number of trunk stents >1, operation time >58.5 minutes, and contrast medium volume >75 mL were risk factors for PIS, and the odds ratios of emergency operation, number of trunk stents >1 piece, operation time >58.5 minutes, and contrast medium volume >75 mL were 2.526 (95% confidence interval [CI], 1.530-4.173), 4.651 (95% CI, 2.838-7.624), 3.577 (95% CI, 2.201-5.815), and 7.356 (95% CI, 4.111-13.160), respectively. Follow-up was completed in 98.5% (532/540) of the patients, with a median follow-up of 67 months (IQR, 50-86 months). There was no significant difference in survival between the PIS and non-PIS groups (12.4% vs 10.3%; P = .476) during follow-up. The incidences of DRCs (7.8% vs 11.6%; P = .200) and aortic false lumen thrombosis (75.8% vs 79.2%; P = .399) were comparable between the PIS and non-PIS groups. Univariate logistic regression analysis showed that PIS had no effect on long-term follow-up mortality, DRCs, entry flow, or aortic false lumen thrombosis rate. CONCLUSIONS: PIS is relatively common after TEVAR and emergency surgery; number of trunk stents >1, operation time >58.5 minutes, and contrast medium volume >75 mL are of high predictive value for the assessment of PIS after TEVAR. However, PIS had little effect on early and late postoperative mortality or DRCs.

10× single-cell sequencing revealed cellular composition heterogeneity in cardiac myxoma with malignant glandular properties.

Cardiac myxoma is the most common primary cardiac tumor in adults. The histogenesis and cellular composition of myxoma are still unclear. This study aims to reveal the role of myxoma cell components and their gene expression in tumor development. We obtained single living cells by enzymatic digestion of tissues from 4 cases of surgically resected cardiac myxoma. Of course, there was 1 case of glandular myxoma and 3 cases of nonglandular myxoma. Then, 10× single-cell sequencing was performed. We identified 12 types and 11 types of cell populations in glandular myxoma and nonglandular myxoma, respectively. Heterogeneous epithelial cells are the main components of glandular myxoma. The similarities and differences in T cells in both glandular and nonglandular myxoma were analyzed by KEGG and GO. The most important finding was that there was active communication between T cells and epithelial cells. These results clarify the possible tissue occurrence and heterogeneity of cardiac myxoma and provide a theoretical basis and guidance for clinical diagnosis and treatment.

Electro-absorption modulated 53 Gbps widely tunable laser based on half-wave V-coupled cavities.

In this paper, a 53 Gbps widely tunable transmitter is experimentally demonstrated for the first time, to our knowledge. An InGaAlAs/InP multiple-quantum-well (MQW) wafer is used with an identical layer structure for both the V-coupled cavity laser (VCL) and the electro-absorption modulator (EAM). The VCL uses a shallow-etched waveguide to reduce loss, while the EAM uses a deep-etched waveguide to increase the 3-dB modulation bandwidth. With the temperature varying from 19.5 to 30°C, the transmitter achieves wavelength tuning of 42 channels with a spacing of 100 GHz, corresponding to a tuning range of 32.6 nm from 1538.94 to 1571.54 nm. The static extinction ratio (ER) for all channels is higher than 14 dB. The measured 3-dB electro-optic (E0) bandwidth of the transmitter is over 40 GHz, which fits well with the calculated 3-dB bandwidth. At a fixed peak-to-peak driving voltage of 2.4 V, all channels exhibit clearly an open eye diagram with a 53 Gbps non-return-to-zero (NRZ) signal, while the dynamic ER is higher than 4.5 dB.

A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.

Detectability of Single Spinless Stellar-Mass Black Holes through Gravitational Lensing of Gravitational Waves with Advanced LIGO.

We investigate the detectability of gravitational waves that have been lensed by a spinless stellar-mass black hole, with respect to the advanced LIGO. By solving the full relativistic linear wave equations in the spacetime of a Schwarzschild black hole, we find that the strong gravity can create unique signals in the lensed waveform, particularly during the merger and ring-down stages. The differences in terms of fitting factor between the lensed waveform and best-fitted unlensed general relativity template with spin precession and higher-order multipoles are greater than 5% for the lens black hole mass within 70M_{⊙}