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Abstract The lower respiratory tract (LRT) microbiome impacts human health, especially among critically ill patients. However, comprehensive characterizations of the LRT microbiome remain challenging due to low microbial mass and host contamination. We develop a chelex100-based low-biomass microbial-enrichment method (CMEM) that enables deep metagenomic profiling of LRT samples to recover near-complete microbial genomes. We apply the method to 453 longitudinal LRT samples from 157 intensive care unit (ICU) patients in three geographically distant hospitals. We recover 120 high-quality metagenome-assembled genomes (MAGs) and associated plasmids without culturing. We detect divergent longitudinal microbiome dynamics and hospital-specific dominant opportunistic pathogens and resistomes in pneumonia patients. Diagnosed pneumonia and the ICU stay duration were associated with the abundance of specific antibiotic-resistance genes (ARGs). Moreover, CMEM can serve as a robust tool for genome-resolved analyses. MAG-based analyses reveal strain-specific resistome and virulome among opportunistic pathogen strains. Evolutionary analyses discover increased mobilome in prevailing opportunistic pathogens, highly conserved plasmids, and new recombination hotspots associated with conjugative elements and prophages. Integrative analysis with epidemiological data reveals frequent putative inter-patient strain transmissions in ICUs. In summary, we present a genome-resolved functional, transmission, and evolutionary landscape of the LRT microbiota in critically ill patients.

Abstract The groove density mismatching of compression gratings, an often-neglected key issue, can induce significant spatiotemporal aberrations especially for super-intense femtosecond lasers. We mainly investigate the angular chirp and the consequent degradation of the effective focused intensity introduced by the groove density mismatching of compression gratings in ultra-intense femtosecond lasers. The results indicate that the tolerances of grating groove density mismatching will rapidly decrease with the beam aperture or spectral bandwidth increases. For our 100PW laser under construction, the grating groove density mismatching should be as small as 0.001 gr/mm if the drop of effective focused intensity has to be controlled below 15%. More importantly, new angular chirp compensation schemes are proposed for both double-grating and four-grating compressors. This work reveals the importance of groove density matching of compression gratings, and can provide helpful guidelines for the design of ultra-intense femtosecond lasers.

The mode conversion efficiency (CE) of the relativistic Laguerre–Gaussian (LG) laser is researched in detail within the context of current petawatt laser facilities. The topological charge, radial integer, laser central wavelength, laser bandwidth, and the design of reflective phase plate are integrated into a unified equation in theory. It is found that the vortex laser mode can be expanded as a series of LG modes, with calculations indicating that the LG10 mode predominates, constituting ∼78% of the total mode distribution. Our analysis reveals that mode CE tends toward a saturation value as the number of steps of the reflective phase plate increases. The 32-step phase plate utilized in relativistic systems is fine enough to obtain a higher CE for LG10 mode lasers, which is also verified in three-dimensional particle-in-cell simulations. This research holds promise for optimizing the design of reflective phase plates to enhance the conversion efficiency of intense LG lasers, thereby facilitating broader applications in intense vortex laser technologies.

We introduce a broadband tunable femtosecond laser source in the long-wave infrared (LWIR) band, covering the range of 5–13.5 μm, based on the integration of optical parametric amplification and difference frequency generation techniques. We utilize a dual-stage tuning method, combined with the high nonlinear coefficient and broadband phase matching range of the BaGa4Se7 crystal, to facilitate significant improvements in spectral coverage and energy efficiency. The laser yields a peak output energy of 43 μJ and maintains energies above 10 μJ across the entire tuning range, with an average power output exceeding 10 mW. The pulse duration at the central wavelength of 8.3 μm is measured at 72 fs full width at half-maximum using the electro-optic sampling method. This LWIR femtosecond laser can be used in many applications, such as molecular fingerprint spectral analysis, ultrafast chemical reaction spectral analysis, materials science, and ultrafast physics research, providing an important research basis for the generation and application of mid-infrared ultrafast laser sources.

Abstract Supercontinuum (SC) light source has advanced ultrafast laser spectroscopy in condensed matter science, biology, physics, and chemistry. Compared to the frequently used photonic crystal fibers and bulk materials, femtosecond laser filamentation in gases is damage-immune for supercontinuum generation. A bottleneck problem is the strong jitters from filament induced self-heating at kHz repetition rate level. We demonstrated stable kHz supercontinuum generation directly in air with multiple mJ level pulse energy. This was achieved by applying an external DC electric field to the air plasma filament. Beam pointing jitters of the 1 kHz air filament induced SC light were reduced by more than 2 fold. The stabilized high repetition rate laser filament offers the opportunity for stable intense SC generation and its applications in air.

Brillouin fiber laser with the non-resonance pumping configuration, has compact set-up, good wavelength tunability and high-power single-frequency-emission capability, being regarded as an important technique for highly-coherent light generation. Such Brillouin fiber lasers, using single-mode fiber (SMF) as the Brillouin gain medium, generally have high lasing thresholds and mode-hopping instabilities, resulting from the relatively-low Brillouin gain coefficient of the conventional SMF. Here, we report a compact, non-resonance-pumping Brillouin photonic crystal fiber laser that can generate kHz-level-linewidth single-frequency lasing with tens-of-mW lasing threshold. Mode-hopping instability of this laser is largely suppressed thanks to the short (∼20 m) cavity length, which gives rise to a free-spectral-range (FSR) value of ∼10 MHz properly matching the tens-of-MHz Brillouin gain bandwidth. Experimental results of both self-heterodyne and frequency-noise measurements indicate a laser linewidth of ∼1.4 kHz, corresponding to high linewidth-narrowing ratio of ∼18. No lasing line of high-order Stokes was observed in experiments as the laser pump power was gradually increased to ∼200 mW, giving a nearly-linear lasing slope.

A vortex retarder (VR) is a widely-used optical component for converting Gaussian light beams into vortex beams, exhibiting unique advantages in a few broadband applications. However, the quality of the vortex beam generated using a VR-based system is highly dependent on the polarization state of the incident light. In this letter, we investigate both theoretically and experimentally the distortion of the output vortex light field resulting from the misalignment of the light polarization state in a VR-based vortex-beam-generation system. While a theoretical model was constructed to study the optical properties of the generated vortex beams at different polarization states of the incident Gaussian beams, systematic characterizations on near- and far-field profiles of the vortex light fields were performed in the experiment. The results exhibit that non-ideal circularly-polarized incident light can introduce a sinusoidal-shape modulation on the optical field, resulting in both phase and intensity distortions of the generated vortex light beam. Our findings provide some insights into the generation and propagation processes of vortex light fields, which could be useful for the practical construction of a VR-based vortex-beam generation system.

Abstract Aim Hydrogels with excellent biocompatibility and biodegradability can be used as the desirable dressings for the therapy of diabetic foot ulcer (DFU). This review aimed to summarize the biological functions of hydrogels, combining with the pathogenesis of DFU. Methods The studies in the last 10 years were searched and summarized from the online database PubMed using a combination of keywords such as hydrogel and diabetes. The biological functions of hydrogels and their healing mechanism on DFU were elaborated. Results In this review, hydrogels were classified by their active substances such as drugs, cytokines, photosensitizers, and biomimetic peptide. Based on this, the biological functions of hydrogels were summarized by associating the pathogenesis of DFU, including oxidative stress, chronic inflammation, cell phenotype change, vasculopathy, and infection. This review also pointed out some of the shortcomings of hydrogels in present researches. Conclusions Hydrogels were classified into carrier hydrogels and self‐functioning hydrogels in this review. Besides, the functions and components of existing hydrogels were clarified to provide assistance for future researches and clinical applications.

BackgroundGastrointestinal (GI) function is critical for patients in intensive care units (ICUs). Whether and how much critically ill patients without GI primary diseases benefit from abdominal physical examinations remains unknown. No evidence from big data supports its possible additive value in outcome prediction.MethodsWe performed a big data analysis to confirm the value of abdominal physical examinations in ICU patients without GI primary diseases. Patients were selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database and classified into two groups depending on whether they received abdominal palpation and auscultation. The primary outcome was the 28-day mortality. Statistical approaches included Cox regression, propensity score matching, and inverse probability of treatment weighting. Then, the abdominal physical examination group was randomly divided into the training and testing cohorts in an 8:2 ratio. And patients with GI primary diseases were selected as the validation group. Several machine learning algorithms, including Random Forest, Gradient Boosting Decision Tree, Adaboost, Extra Trees, Bagging, and Multi-Layer Perceptron, were used to develop in-hospital mortality predictive models.ResultsAbdominal physical examinations were performed in 868 (2.63%) of 33,007 patients without primary GI diseases. A significant benefit in terms of 28-day mortality was observed among the abdominal physical examination group (HR 0.75, 95% CI 0.56–0.99; p = 0.043), and a higher examination frequency was associated with improved outcomes (HR 0.62, 95%CI 0.40–0.98; p = 0.042). Machine learning studies further revealed that abdominal physical examinations were valuable in predicting in-hospital mortality. Considering both model performance and storage space, the Multi-Layer Perceptron model performed the best in predicting mortality (AUC = 0.9548 in the testing set and AUC = 0.9833 in the validation set).ConclusionConducting abdominal physical examinations improves outcomes in critically ill patients without GI primary diseases. The results can be used to predict in-hospital mortality using machine learning algorithms.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has affected billions of people worldwide, and the lessons learned need to be concluded to get better prepared for the next pandemic. Early identification of high-risk patients is important for appropriate treatment and distribution of medical resources. A generalizable and easy-to-use COVID-19 severity stratification model is vital and may provide references for clinicians.MethodsThree COVID-19 cohorts (one discovery cohort and two validation cohorts) were included. Longitudinal peripheral blood mononuclear cells were collected from the discovery cohort (n = 39, mild = 15, critical = 24). The immune characteristics of COVID-19 and critical COVID-19 were analyzed by comparison with those of healthy volunteers (n = 16) and patients with mild COVID-19 using mass cytometry by time of flight (CyTOF). Subsequently, machine learning models were developed based on immune signatures and the most valuable laboratory parameters that performed well in distinguishing mild from critical cases. Finally, single-cell RNA sequencing data from a published study (n = 43) and electronic health records from a prospective cohort study (n = 840) were used to verify the role of crucial clinical laboratory and immune signature parameters in the stratification of COVID-19 severity.ResultsPatients with COVID-19 were determined with disturbed glucose and tryptophan metabolism in two major innate immune clusters. Critical patients were further characterized by significant depletion of classical dendritic cells (cDCs), regulatory T cells (Tregs), and CD4+ central memory T cells (Tcm), along with increased systemic interleukin-6 (IL-6), interleukin-12 (IL-12), and lactate dehydrogenase (LDH). The machine learning models based on the level of cDCs and LDH showed great potential for predicting critical cases. The model performances in severity stratification were validated in two cohorts (AUC = 0.77 and 0.88, respectively) infected with different strains in different periods. The reference limits of cDCs and LDH as biomarkers for predicting critical COVID-19 were 1.2% and 270.5 U/L, respectively.ConclusionOverall, we developed and validated a generalizable and easy-to-use COVID-19 severity stratification model using machine learning algorithms. The level of cDCs and LDH will assist clinicians in making quick decisions during future pandemics.

Abstract A high-brightness ultrabroadband supercontinuum white laser is desirable for various fields of modern science. Here, we present an intense ultraviolet-visible-infrared full-spectrum femtosecond laser source (with 300–5000 nm 25 dB bandwidth) with 0.54 mJ per pulse. The laser is obtained by sending a 3.9 μm, 3.3 mJ mid-infrared pump pulse into a cascaded architecture of gas-filled hollow-core fiber, a bare lithium niobate crystal plate, and a specially designed chirped periodically poled lithium niobate crystal, under the synergic action of second and third order nonlinearities such as high harmonic generation and self-phase modulation. This full-spectrum femtosecond laser source can provide a revolutionary tool for optical spectroscopy and find potential applications in physics, chemistry, biology, material science, industrial processing, and environment monitoring.

Abstract Compressing high-energy laser pulses to a single-cycle and realizing the “λ 3 laser concept”, where λ is the wavelength of the laser, will break the current limitation of super-scale projects and contribute to the future 100-petawatt and even Exawatt lasers. Here, we have realized ultra-broadband gold gratings, core optics in the chirped pulse amplification, in the 750–1150 nm spectral range with a > 90% −1 order diffraction efficiency for near single-cycle pulse stretching and compression. The grating is also compatible with azimuthal angles from −15° to 15°, making it possible to design a three-dimensional compressor. In developing and manufacturing processes, a crucial grating profile with large base width and sharp ridge is carefully optimized and controlled to dramatically broaden the high diffraction efficiency bandwidth from the current 100–200 nm to over 400 nm. This work has removed a key obstacle to achieving the near single-cycle 100-PW lasers in the future.

A novel method, combining an asymmetric four-grating compressor (AFGC) with pulse post-compression, is numerically demonstrated to improve the spatial uniformity of laser beams and hence to suppress small-scale self-focusing (SSSF) during the beam propagation in nonlinear materials of high peak power lasers. The spatial uniformity of laser beams is an important factor in performing post-compression, due to the spatial intensity modulation, or hot spots will be aggravated during the nonlinear propagation and then seriously damage the subsequent optical components. Three-dimensional numerical simulations of post-compression are implemented based on a femtosecond laser with a standard compressor and an AFGC, respectively. The simulated results indicate that post-compression with the AFGC can efficiently suppress the SSSF and also shorten the laser pulses from 30 fs to sub-10 fs. This work can provide a promising route to overcome the challenge of SSSF and will be meaningful to promote the practical application of the post-compression technique in high peak power lasers.

Cell migration–inducing protein (CEMIP), also known as KIAA1199 and hyaluronan-binding protein involved in hyaluronan depolymerization, is a new member of the hyaluronidase family that degrades hyaluronic acid (HA) and remodels the extracellular matrix. In recent years, some studies have reported that CEMIP can promote the proliferation, invasion, and adhesion of various tumor cells and can play an important role in bacterial infection and arthritis. This review focuses on the pathological mechanism of CEMIP in a variety of diseases and expounds the function of CEMIP from the aspects of inhibiting cell apoptosis, promoting HA degradation, inducing inflammatory responses and related phosphorylation, adjusting cellular microenvironment, and regulating tissue fibrosis. The diagnosis and treatment strategies targeting CEMIP are also summarized. The various functions of CEMIP show its great potential application value.

In this submission, we report a maximum 638-W fiberized chirped-pulse-amplification (CPA) laser system with a bulk reflection grating compressor. The system is able to emit 338-W compressed pulses of 624 fs centered at 1 µm, corresponding to a pulse energy of 1.3 µJ at a pulse repetition rate of 258 MHz. The output beam quality factor M2 is measured to be

Space-time wave packets are optical pulses synthesized from light waves carrying strong correlations between their spatial and temporal degrees of freedom and show many anomalous behaviors such as superluminal propagation. In this study, the authors proposed a way of amplifying space-time wave packets by nonlinear optical parametric processes, which will widen the applications of the new optical wave packets.

Abstract The group-velocity of the propagation-invariant optical wave-packet generated by the conical superposition can be controlled by introducing well-designed arbitrarily-axisymmetric pulse-front deformation, which permits realizing superluminal, subluminal, accelerating, decelerating, and even nearly-programmable group-velocities. To better understand the tunability of the group-velocity, the generation methods of this propagation-invariant optical wave-packet and the mechanisms of the tunable group-velocity in both the physical and Fourier spaces are investigated. We also have studied the relationship with the recently-reported space–time wave-packet, and this group-velocity-tunable propagation-invariant optical wave-packet should be a subset of the space–time wave-packet.

Micro-structured targets can be employed to enhance the coupling of laser energy to the high energy density plasma. Here we report on experimental measurement of enhanced proton beam energy from laser-driven micro-wire array (MWA) targets along the backward direction. An ultra-intense (∼2×1020W/cm2) laser pulse of ∼ 40 fs pulse duration interacts with the MWA structure and induces large population of energetic electrons. The enhanced sheath field efficiently accelerates protons both transversely and longitudinally. The spectrometers record proton cut-off energy of around 16 MeV and temperature 813keV along the backward direction, which is 20%−60% higher than that of a flat target under commensurate laser conditions. Comparison with particle-in-cell simulations suggests that the enhancement originates from the increased temperature and population of the hot electrons within the micro-wires. These measurements provide a direct probe of the high energy density plasma condition in laser-driven solid targets and a useful benchmark for further studies on laser-driven micro-structured targets.

Novel phase-locked acceleration of a relativistic isolated attosecond electron sheet was realized using a relativistic reflected spatiotemporal optical vortex (STOV) pulse in three-dimensional particle-in-cell simulations. Electrons can be trapped in a spatiotemporal phase singularity within the STOV pulse center, modulated into an approximately 600-attosecond duration sheet. Furthermore, electrons can be phase-locked accelerated to the order of GeV in the longitudinal direction. Such an isolated attosecond electron sheet driven by the intense STOV pulse can be used in isolated attosecond pulse generation, ultrashort x/γ-ray radiation, and attosecond electron diffraction.

In quest of achieving compact and economic PW-level Ti:Sapphire (Ti:sa) lasers with a sub-15 fs pulse duration, a modified hybrid amplification scheme, which combines the optical parametric chirped pulse amplifier (OPCPA) and the chirped pulse amplifier (CPA), is presented and numerically investigated in this paper. The key characteristic of this scheme is that the conventional Ti:sa regenerative amplifier and preamplifier are replaced by a dual-crystal OPCPA front-end, which is spectrally matched with the upstream seed source and the downstream Ti:sa amplifiers and, therefore, can realize a broader spectrum. Moreover, some useful laser techniques are also applied to suppress the spectral gain narrowing and redshift in the Ti:sa CPA chain and to control the residual dispersion in the laser system. This way, fewer amplification stages and pump lasers are required to reach PW-level peak power compared with traditional all-CPA Ti:sa lasers. Numerical results indicate that pulse energy and spectral bandwidth can reach up to ∼22 J and ∼125 nm at full width at half maximum (FWHM), respectively, only by employing three-stage amplifiers. After compression, PW-level lasers with a ∼13.3 fs pulse duration are expected. This work can offer a promising route for the development of compact and economic PW-level Ti:sa lasers.

Traumatic brain injury (TBI), a major global health burden, disrupts the neurological system due to accidents and other incidents. While the Glasgow coma scale (GCS) gauges neurological function, it falls short as the sole predictor of overall mortality in TBI patients. This highlights the need for comprehensive outcome prediction, considering not just neurological but also systemic factors. Existing approaches relying on newly developed biomolecules face challenges in clinical implementation. Therefore, we investigated the potential of readily available clinical indicators, like the blood urea nitrogen-to-albumin ratio (BAR), for improved mortality prediction in TBI. In this study, we investigated the significance of the BAR in predicting all-cause mortality in TBI patients. In terms of research methodologies, we gave preference to machine learning methods due to their exceptional performance in clinical support in recent years. Initially, we obtained data on TBI patients from the Medical Information Mart for Intensive Care database. A total of 2602 patients were included, of whom 2260 survived and 342 died in hospital. Subsequently, we performed data cleaning and utilized machine learning techniques to develop prediction models. We employed a ten-fold cross-validation method to obtain models with enhanced accuracy and area under the curve (AUC) (Light Gradient Boost Classifier accuracy, 0.905 ± 0.016, and AUC, 0.888; Extreme Gradient Boost Classifier accuracy, 0.903 ± 0.016, and AUC, 0.895; Gradient Boost Classifier accuracy, 0.898 ± 0.021, and AUC, 0.872). Simultaneously, we derived the importance ranking of the variable BAR among the included variables (in Light Gradient Boost Classifier, the BAR ranked fourth; in Extreme Gradient Boost Classifier, the BAR ranked sixth; in Gradient Boost Classifier, the BAR ranked fifth). To further evaluate the clinical utility of BAR, we divided patients into three groups based on their BAR values: Group 1 (BAR < 4.9 mg/g), Group 2 (BAR ≥ 4.9 and ≤10.5 mg/g), and Group 3 (BAR ≥ 10.5 mg/g). This stratification revealed significant differences in mortality across all time points: in-hospital mortality (7.61% vs. 15.16% vs. 31.63%), as well as one-month (8.51% vs. 17.46% vs. 36.39%), three-month (9.55% vs. 20.14% vs. 41.84%), and one-year mortality (11.57% vs. 23.76% vs. 46.60%). Building on this observation, we employed the Cox proportional hazards regression model to assess the impact of BAR segmentation on survival. Compared to Group 1, Groups 2 and 3 had significantly higher hazard ratios (95% confidence interval (CI)) for one-month mortality: 1.77 (1.37–2.30) and 3.17 (2.17–4.62), respectively. To further underscore the clinical potential of BAR as a standalone measure, we compared its performance to established clinical scores, like sequential organ failure assessment (SOFA), GCS, and acute physiology score III(APS-III), using receiver operator characteristic curve (ROC) analysis. Notably, the AUC values (95%CI) of the BAR were 0.67 (0.64–0.70), 0.68 (0.65–0.70), and 0.68 (0.65–0.70) for one-month mortality, three-month mortality, and one-year mortality. The AUC value of the SOFA did not significantly differ from that of the BAR. In conclusion, the BAR is a highly influential factor in predicting mortality in TBI patients and should be given careful consideration in future TBI prediction research. The blood urea nitrogen-to-albumin ratio may predict mortality in TBI patients.

Background: Recent studies suggest that acute kidney injury (AKI) can be treated with renal replacement therapy (RRT). However, its benefits to patients with sepsis-associated AKI (SA-AKI), which is linked to high mortality and morbidity rates, remain under debate. The aim of this study was to compare the outcomes of different RRT strategies for patients with SA-AKI. Methods: This retrospective study evaluated patients who were admitted to the hospital with sepsis and developed SA-AKI during hospitalization from 1st January 2014 to 31st January 2019. Mortality, renal recovery, and systemic organ function at 90 days following admission were compared between the RRT group (RG) and non-RRT group (NRG), as well as the early-RRT group (EG) and delayed-RRT group (DG). The groups were defined according to the time from admission to RRT initiation (criterion 1, EG1 and DG1) and Kidney Disease Improving Global Outcomes (KDIGO) classification (criterion 2, EG2 and DG2). Categorical and continuous variables were compared using the chi-squared test or Fisher's exact test and Student's t-test or Wilcoxon test. Kaplan–Meier curves were constructed to determine the unadjusted survival rates for the different subgroups. Results: A total of 116 patients were included in this study; of those, 38 received RRT and 46 expired within 90 days. Among different strategies of RRT, there were no significant differences found in 90-day mortality (RG vs. NRG: χ2=0.610, P=0.435; EG1 vs. DG1: χ2 =0.835, P=0.360; EG2 vs. DG2: χ2=0.022, P=0.899) and renal recovery. However, the values of change in sequential organ failure assessment (ΔSOFA)max–min of patients in the EG and RG were significantly higher than those recorded in the NRG (ΔSOFARG=7.0, ΔSOFANRG=3.60, ΔSOFAEG1=9.00, ΔSOFAEG2=6.30; P

The performance of laser-driven ion accelerators is intimately linked to the structure of the target. Here, laser-proton acceleration from a 3D-printed microwire-array target boosts the conversion efficiency and cut-off energy compared to a flat foil.

Abstract Femtosecond laser ablation has been demonstrated to be a versatile tool to produce micro/nanoscale features with high precision and accuracy. However, the use of high laser fluence to increase the ablation efficiency usually results in unwanted effects, such as redeposition of debris, formation of recast layer, and heat‐affected zone in or around the ablation craters. Here this limitation is circumvented by exploiting a thin frost layer with a thickness of tens of microns, which can be directly formed by the condensation of water vapor from the air onto the exposed surface whose temperature is below the freezing point. When the femtosecond laser beam is focused onto the target surface covered with a thin frost layer, only the local frost layer around the laser‐irradiated spot melts into water, helping to boost ablation efficiency, suppress the recast layer, and reduce the heat‐affect zone, while the remaining frost layer can prevent ablation debris from adhering to the target surface. By this frost‐assisted strategy, high‐quality surface micro/nano‐structures are successfully achieved on both plane and curved surfaces at high laser fluences, and the mechanism behind the formation of high‐spatial‐frequency (HSF) laser‐induced periodic surface structures (LIPSSs) on silicon is discussed.

Cumulative effects are crucial for applications of laser filaments, such as for the remote transfer of energy and the control of electric discharges. Up to now, studies of cumulative effects in the air of high‐repetition‐rate pulse trains have been performed at lower rates than 10 kHz. Herein, the nonlinear effects associated with short plasma filaments produced by pulses of moderate energy (0.4 mJ per pulse) and repetition rates up to 100 kHz are experimentally characterized. With increasing repetition rate, a decrease in absorption, fluorescence emission, and breakdown voltage and concurrently an increase in peak intensity and third‐harmonic‐generation efficiency are observed. Hydrodynamic simulations of the heated gas show that the observed decreases are directly related to a quasi‐stationary state of reduced gas density in the filament. However, further investigations are required to fully understand the physics underpinning the observed sharp reduction of the breakdown voltage at 100 kHz repetition rates. The results may prove relevant for energy and information delivery applications by laser‐induced air waveguide or electric discharge and lightning control.

Terahertz radiation can provide unprecedented vistas in physical studies such as transient matter state control and advanced free-electron manipulation. Here, we present one feasible path towards high-repetition-rate, intense THz sources by combining the wire-based THz source on a consecutively running, wire-conveying tape design. The proof-of-principle experimental results show an upper 30 mW average THz power output under 1 kHz laser excitation, which presents the first high-repetition-rate, and most importantly, portable and application in handy THz source that is generated by solid plasmas. The generated THz pulses are characterized with a 0.3 THz center frequency and ∼0.3 THz bandwidth. We believe this tabletop laser-driven high-repetition-rate THz source will open a new door for THz and related interdisciplinary sciences.

As a driving source for many nonlinear vortex phenomena, such as the generation of isolated attosecond optical vortices, terahertz vortices, etc., terawatt-class few-cycle short-wave infrared vortex lasers are now attracting widespread attention. However, because the vortex characteristics of optical vortices are difficult to maintain in the amplification and compression stages, the generation of high-intensity few-cycle vortex lasers is still in the exploratory stage. In this article, we report 20-Hz, 18.6-mJ, 60-fs, and 1.45-μm infrared vortex lasers with 1, 2, and 3 topological charges successfully generated in an optical parametric chirped pulse amplification system. A clean intensity node at the beam center is observed and highly stable propagation in free space is demonstrated. Moreover, this high-energy vortex pulse is spectrally broadened in multiple thin plates and temporally compressed to 10.59 fs (2.2 optical cycles) with chirped mirrors, corresponding to a peak power of 1.08 TW, while highly preserving the vortex information. We believe that the generated high-energy few-cycle vortex laser has important applications from vortex optics to strong-field physics.

With the development of high-volume manufacturing for very-large-scale integrated circuits, the purity of the light source in the extreme ultraviolet lithography (EUVL) system needs to fulfil extreme requirements in order to avoid thermal effect, optical distortion and critical dimension errors caused by out-of-band radiations. This paper reviews the key technologies and developments of the spectral purity systems for both a free-standing system and a built-in system integrated with the collector. The main challenges and developing trends are also discussed, with a view towards practical applications for further improvement. Designing and manufacturing spectral purity systems for EUVL is not a single task; rather, it requires systematic considerations for all relevant modules. Moreover, the requirement of spectral purity filters drives the innovation in filtering technologies, optical micromachining and advanced metrology.

The development of high-intensity ultrafast laser facilities provides the possibility to create novel physical phenomena and matter states. The timing fluctuation of the laser pulses is crucial for pump–probe experiments, which is one of the vital means to observe the ultrafast dynamics driven by intense laser pulses. In this paper, we demonstrate the timing fluctuation characterization and control of the front end of a 100-PW laser that is composed of a high-contrast optical parametric amplifier (seed) and a 200-TW optical parametric chirped pulse amplifier (preamplifier). By combining the timing jitter measurement with a feedback system, the laser seed and preamplifier are synchronized to the reference with timing fluctuations of 1.82 and 4.48 fs, respectively. The timing system will be a key prerequisite for the stable operation of 100-PW laser facilities and provide the basis for potential pump–probe experiments performed on the laser.

As intense, ultrashort, kHz-repetition-rate laser systems become commercially available, pulse cumulative effects are critical for laser filament-based applications. In this work, the pulse repetition-rate effect on femtosecond laser filamentation in air was investigated both numerically and experimentally. The pulse repetition-rate effect has negligible influence at the leading edge of the filament. Clear intensity enhancement from a high-repetition pulse is observed at the peak and tailing edge of the laser filament. As the repetition rate of the laser pulses increases from 100 to 1000 Hz, the length of the filament extends and the intensity inside the filament increases. A physical picture based on the pulse repetition-rate dependent ‘low-density hole’ effect on filamentation is proposed to explain the obtained results well.

A single-shot measurement of electron emittance was experimentally accomplished using a focused transfer line with a dipole. The betatron phase of electrons based on laser wakefield acceleration (LWFA) is energy dependent owing to the coupling of the longitudinal acceleration field and the transverse focusing (defocusing) field in the bubble. The phase space presents slice information after phase compensation relative to the center energy. Fitting the transverse size of the electron beam at different energy slices in the energy spectrum measured 0.27 mm mrad in the experiment. The diagnosis of slice emittance facilitates local electron quality manipulation, which is important for the development of LWFA-based free electron lasers. The quasi-3D particle-in-cell simulations matched the experimental results and analysis well.

Abstract The exposome depicts the total exposures in the lifetime of an organism. Human exposome comprises exposures from environmental and humanistic sources. Biological, chemical, and physical environmental exposures pose potential health threats, especially to susceptible populations. Although still in its nascent stage, we are beginning to recognize the vast and dynamic nature of the exposome. In this review, we systematically summarize the biological and chemical environmental exposomes in three broad environmental matrices—air, soil, and water; each contains several distinct subcategories, along with a brief introduction to the physical exposome. Disease‐related environmental exposures are highlighted, and humans are also a major source of disease‐related biological exposures. We further discuss the interactions between biological, chemical, and physical exposomes. Finally, we propose a list of outstanding challenges under the exposome research framework that need to be addressed to move the field forward. Taken together, we present a detailed landscape of environmental exposome to prime researchers to join this exciting new field.

Nanomedicine 2.0 refers to the next generation of nanotechnology-based medical therapies and diagnostic tools. This field focuses on the development of more sophisticated and precise nanoparticles (NPs) for targeted drug delivery, imaging, and sensing. It has been established that the nuclear delivery of NP-loaded drugs can increase their therapeutic efficacy. To effectively direct the NPs to the nucleus, the attachment of nuclear localization signals (NLSs) to NPs has been employed in many applications. In this review, we will provide an overview of the structure of nuclear pore complexes (NPCs) and the classic nuclear import mechanism. Additionally, we will explore various nanoparticles, including their synthesis, functionalization, drug loading and release mechanisms, nuclear targeting strategies, and potential applications. Finally, we will highlight the challenges associated with developing nucleus-targeted nanoparticle-based drug delivery systems (NDDSs) and provide insights into the future of NDDSs.

ABSTRACT Emerging evidence shows that modulation of the microbiome can suppress intra-abdominal hypertension (IAH)-induced intestinal barrier damage through the regulation of amino acid (AA) biosynthesis. Here, we investigated the protective effects of orally gavaged Lactobacillus acidophilus L-92 (L92) and a mixture of AA in rats with induced IAH. The results showed that both L92 and AA pretreatments effectively mitigated IAH-induced intestinal damage. Interestingly, L92 but not AA prevented metagenomic changes induced by IAH. Bacteroides fragilis, Bacteroides eggerthii, Bacteroides ovatus, Faecalibacterium prausnitzii, Prevotella, and extensively altered functional pathways were associated with L92-mediated host protection. Metabolomic profiling revealed that tryptophan metabolism was involved in both L92- and AA-mediated gut protection. The tryptophan metabolite 5-hydroxyindoleacetic acid (5-HIAA) is a sensitive biomarker for IAH in rats and patients with either gut-derived sepsis (n = 41) or all-source sepsis (n = 293). In conclusion, we show that microbiome and metabolic modulations can effectively prevent IAH-induced intestinal damage and that 5-HIAA is a potential metabolic marker for IAH and sepsis. IMPORTANCE Gut protection through modulation of the microbiome for critically ill patients has been gaining much attention recently. Intra-abdominal hypertension (IAH) is a prevailing clinical feature of acute gastrointestinal injuries in critically ill patients, characterized by nonspecific intestinal barrier damage. Prolonged IAH can induce or aggravate the development of sepsis and multiorgan dysfunctions. Therefore, the prevention of IAH-induced damage in rats through microbiome and metabolic interventions by commercially available L92 and AA treatments and the identification of 5-HIAA as an important marker for IAH/sepsis have important clinical implications for the treatment and early diagnosis of critically ill patients.

In attosecond and strong-field physics, the acquisition of few-cycle laser sources open up a new area. We report a nonlinear pulse compression technology combining multi-thin-plate spectral broadening and nonlinear self-compression that generates a 0.52 mJ, good spatial quality characteristics and a spectral bandwidth supporting a 14 fs Fourier transform limited duration at 1 kHz repetition rate and at a center wavelength of 1.9 μm. The total energy transfer efficiency is up to 83%. Pulse to pulse stability of the energy output is 0.7% (RMS). The pulse duration is near 3 optical cycles. This pulse compression approach can be a key-enabling technology for the next generation of extreme photonics, attosecond research and coherent x ray-science, and it also can be further extended to mid-infrared lasers with longer wavelengths and higher peak power.

Summary: When a biased electric/light field is applied to centrosymmetric crystals like silicon, the broken symmetry creates even-order harmonics radiation which can reveal key insights into the material. Recently, the second harmonic has been generated by THz-induced symmetry breaking, but the observation of higher-order radiation remains largely unexplored. Here, we demonstrate picosecond-level ultrafast, nondestructive symmetry manipulation of silicon crystal by using a 500 kV/cm intense terahertz (THz) electric field. The THz-induced fourth harmonic of the infrared probe is also observed and characterized for the first time. In addition, we find that the even-order harmonics show no dependence on the THz field direction thus it allows for sub-cycle symmetry manipulations. Our study paves the way toward ultrafast all-optical crystal symmetry control in the future high-speed electronics and photonics.

This narrative review aimed to clarify the characteristics of international government support for sepsis research, trends in published literature on sepsis, and potential contributions of government-source grants to progress in sepsis research between fiscal years 2010 and 2019. The data in this study were collected from the National Institutes of Health (NIH, https://projectreporter.nih.gov/reporter.cfm/ ) of the United States of America (USA), National Natural Science Foundation of China (NSFC, https://isisn.nsfc.gov.cn/egrantweb/ ), and Japan Society for the Promotion of Science (JSPS, https://kaken.nii.ac.jp/ ). All sepsis-related projects approved by the NIH, NSFC, and JSPS were retrieved by searching the project titles, abstracts, and key words for “sepsis,” “septic shock,” or “sepsis inflammatory response syndrome” between 2010 and 2019. Representative sepsis-related studies published between Jan 2010 and Aug 2020 by the first/corresponding authors from these countries were obtained by searching the PubMed database using Medical Subject Heading terms for “sepsis” in representative journals, including Nature , Cell, Science, The Lancet, New England Journal of medicine (New Engl J Med), The Journal of American Medical Association (JAMA), Critical Care Medicine (CCM), Intensive Care Medicine (ICM), Chest, Annals of Emergency Medicine (Ann Emerg Med), and American Thoracic Society journals (ATS). The total/annual institutional budgets, major funding mechanisms and schemes, superior institutions and individual principal investigators, and published original research articles in the field of sepsis in the USA, China, and Japan during the past decade were investigated. The national supporting schemes of the NIH, NSFC, and JSPS were similar. Support from these institutions is quite important for the development of the field of “sepsis” which was acknowledged in 57–64% of original research articles published in CCM. For the future development of precision medicine in sepsis, more government funding support is necessary.

A near-infrared (NIR) supercontinuum and ultrashort pulses are generated via phase-mismatched cascaded frequency conversion in DSTMS (4-N, N-dimethylamino-4'-N'-methyl-stilbazolium 2, 4, 6-trimethylbenzenesulfonate) crystal. NIR pulses with a central wavelength of 1.5 μm and 63 fs pulse duration are incident into the crystal, and the spectrum is broadened to over 1200-2100 nm. Compensating the dispersion by fused silica, ultrashort NIR pulses with 16.6 fs pulse duration are obtained. Meanwhile, intense single-cycle terahertz pulses are generated via optical rectification in DSTMS crystal.

Here, we report the recent progress on the front end developed for the 100 PW-class laser facility. Using 3 stages of optical parametric chirped-pulse amplification (OPCPA) based on lithium triborate (LBO) crystals, we realized a 5.26 J/0.1 Hz amplified output with a bandwidth over 200 nm near the center wavelength of 925 nm. After the compressor, we obtained a pulse duration of 13.4 fs. As the compression efficiency reached 67%, this OPCPA front end could potentially support a peak power of 263 TW at a repetition rate of 0.1 Hz. To the best of our knowledge, among all the 100 TW-level OPCPA systems, it shows the widest spectral width, the shortest pulse duration, and it is also the first OPCPA system working at a repetition-rate mode.

Background: The intensive care unit is a center for massive data collection, making it the best field to embrace big data and artificial intelligence. Objective: This study aimed to provide a literature overview on the development of artificial intelligence in critical care medicine (CCM) and tried to give valuable information about further precision medicine. Methods: Relevant studies published between January 2010 and June 2021 were manually retrieved from the Science Citation Index Expanded database in Web of Science (Clarivate), using keywords. Results: Research related to artificial intelligence in CCM has been increasing over the years. The USA published the most articles and had the top 10 active affiliations. The top ten active journals are bioinformatics journals and are in JCR Q1. Prediction, diagnosis, and treatment strategy exploration of sepsis, pneumonia, and acute kidney injury were the most focused topics. Electronic health records (EHRs) were the most widely used data and the “-omics” data should be integrated further. Conclusions: Artificial intelligence in CCM has developed over the past decade. With the introduction of constantly growing data volume and novel data types, more investigation on artificial intelligence ethics and model correctness and extrapolation should be performed for generalization.

The focusing quality of high peak power lasers plays a crucial role in laser wakefield electron acceleration investigations. We report here an improvement in the focusing quality of the SULF-1PW laser beamline, planning to drive and generate 5~10 GeV electron beams. After the wavefront correction in vacuum with an adaptive optical system and the focusing with an f/56 off-axis parabolic mirror, near-diffraction-limited focal spots with a size of 52 × 54 μm2 at full width at half maximum are achieved, and the enclosed energy inside this size is ~36.6%. Consequently, the focused intensity of ~1.66 × 1019 W/cm2 can be achieved at 1 PW peak power. Moreover, we also examine the wavefront stability in air and vacuum, respectively. From the statistical analysis of 1900 shots of successive laser pulses at 1 Hz, we identify the wavefront fluctuation resulting from air turbulence and the better correction capacity in vacuum. This work demonstrates the importance and necessity of wavefront correction in vacuum for high peak power lasers.

Tellurium has two-dimensional phases and some Weyl nodes around its Femi level that make it a suitable candidate for the study and application in nonlinear optics. Here the authors show the synthesis and use of bio-grown optical Te(0) nanoparticles for optical modulation and thermo-optic switching.

Femtosecond laser filament-generated plasma can generate electromagnetic pulses (EMPs). These pulses may reduce the instrument’s precision, and, hence, influence the accuracy of the experimental results. They may even cause widespread disruption by disabling of the electronic control systems or distribution networks of power plants. This study investigated the characteristics of EMPs generated from the interaction of filament-generated plasmas with a solid target in air. In this study, ultrafast laser filamentation was used to produce plasma, which was focused on a 3 mm-thick aluminum (Al) alloy target for interaction, and the spatial distribution and main contributors of the EMPs were systematically and extensively studied. The results showed that the EMPs generated from ultrafast laser filament interaction with the Al alloy target had the following characteristics: the EMP energy generated from laser filament interaction with solid targets is tens of times higher than that generated only from the femtosecond laser filament; the maximum EMP signals appeared at a 20°–80°detection angle. The relationship between the energy of EMPs and the width and energy of the laser pulses is presented and discussed. These findings are beneficial for gaining insight into the EMP generation mechanism, spatial distribution, and transmission, and for providing more information for the design of EMPs’ shielding.

We report on the experimental investigation of femtosecond laser filament guided negative coronas. When the coupling between the filament and negative corona was weak, the side fluorescence spectral analysis confirmed the existence of impact ionization although less effect on the filament length was observed. When the coupling was strong so that the negative corona was well connected with the filament, the filament guided coronas at the ends of laser filaments were observed. The newly generated negative coronas were confined around the filament axis, and no streamer-type of coronas guided by the filament was observed under conditions similar to those reported in the work of Wang et al. [Sci. Rep. 5, 18681 (2015)] although both could give rise to an elongation of the filament. A physical picture was proposed to understand the processes of the laser filament guided coronas.

The American Joint Committee on Cancer (AJCC) staging system is insufficiently prognostic for gastric cancer (GC) patients and complementary factors are in urgent need. Here we aimed to develop a comprehensive model, consisting of both immune signatures and cancer signaling molecules, which was expected to accurately improve survival prediction in non-metastatic gastric cancer (GC). We first validated the prognostic value of a combination of 18 immune features and 52 cancer-signaling molecules in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Then, their expression and distribution were analyzed in consecutive 1180 GC patients using immunohistochemistry. We developed and validated a novel protein-based prognostic classifier using CDH1, an epithelial–mesenchymal transition (EMT) marker, and five immune features (CD3, CD4, CD274, GZMB, and PAX5) by Cox regression model with group LASSO penalty. We observed significant differences in the overall survival of the high- and low-prognostic risk groups (66.8% VS 27.0%, P

Based on a 6 cm-long two-segment hybrid capillary discharge waveguide, a multi-GeV electron beam with energy up to 3.2 GeV and 9.7% rms energy spread was achieved in a cascaded laser wakefield acceleration scheme, powered by an on-target 210 TW laser pulse. The electron beam was trapped in the first segment via ionization-induced injection, and then seeded into the second segment for further acceleration. The long-distance stable guiding of the laser pulse and suppression of the dark current inside the second-segment capillary played an important role in the generation of high-energy electron beams, as demonstrated by quasi-three-dimensional particle-in-cell simulations.