Genome-wide analysis of two different regions of brain reveals the molecular changes of fertility related genes in rln3a-/- mutants in male Nile tilapia (Oreochromis niloticus).

Relaxin3 (rln3) has been associated with various emotional and cognitive processes, including stress, anxiety, learning, memory, motivational behavior, and circadian rhythm. Notably, previous report revealed that Rln3a played an indispensable role in testicular development and male fertility in Nile tilapia (Oreochromis niloticus). However, the underlying molecular mechanisms remain largely unknown. We found that Rln3a is expressed exclusively in the diencephalon* (Di*) of the brain. Deficiency of Rln3a resulted in a significant increase in serum dopamine level and an upregulation of gene expression of gnrh1 and kisspeptin2. To further elucidate the role of Rln3a in fish fertility, we collected two different regions of Di* and hypothalamus (Hyp) tissues for subsequent RNA-seq analysis of both wild-type (rln3a+/+) and rln3a-/- male tilapia. Upon the transcriptomic data, 1136 and 755 differentially expressed genes (DEGs) were identified in the Di* and Hyp tissues, respectively. In Di*, the up-regulated genes were enriched in circadian rhythm, chemical carcinogenesis, while the down-regulated genes were enriched in type II diabetes mellitus, dopaminergic synapse, and other pathways. In Hyp, the up-regulated genes were enriched in circadian rhythm, pyrimidine metabolism, while the down-regulated genes were enriched in type I diabetes mellitus, autoimmune thyroid disease, and other pathways. Subsequently, the results of both qRT-PCR and FISH assays highlighted a pronounced up-regulation of core circadian rhythm genes, cry1b and per3, whereas genes such as clocka, clockb, and arntl exhibited down-regulation. Furthermore, the genes associated with dopamine biosynthesis were significantly increased in the Hyp. In summary, the mutation of rln3a in male tilapia resulted in notable changes in circadian rhythm and disease-linked signaling pathways in the Di* and Hyp. These changes might account for the fertility defects observed in rln3a-/- male mutants in tilapia.

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles.

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

Effects of Qidan Tangshen Granule on diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: This study aimed to conduct a prospective, randomized, controlled clinical trial using, Qidan Tangshen Granule, a traditional Chinese medicine (TCM), as an antioxidant, to treat diabetic kidney disease (DKD) patients. METHODS: A total of 355 patients were enrolled, and after exclusions, 219 patients were divided into an intervention group (n = 109) receiving Qidan Tangshen Granule treatment and a control group (n = 110) receiving conventional treatment. Demographic and physiological parameters were evaluated at baseline and 3 months and 12 months of follow-up. The levels of serum oxidants including 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 3-nitrotyrosine (3-NT), and the enzymic anti-oxidant, superoxide dismutase (SOD), were evaluated using enzyme-linked immunosorbent assays. RESULTS: Qidan Tangshen Granule treatment significantly reduced hemoglobin A1c (HbA1c) and albumin-to-creatinine ratio (UACR) levels, improved renal function, and exerted antioxidative effects in DKD patients. Compared to the control group, the intervention group showed increased levels of SOD and decreased levels of 8-OHdG and 3-NT, indicating reduced oxidative stress. Furthermore, the intervention group demonstrated a significant decrease in HbA1c and UACR levels and an improvement in glomerular filtration rate compared to the control group. CONCLUSIONS: Qidan Tangshen Granule may be a potential therapeutic option for the treatment of DKD, offering improved clinical outcomes for patients.

Efficient Fabrication of Self-Assembled Polylactic Acid Colloidosomes for Pesticide Encapsulation.

Colloidosomes are microcapsules whose shells are composed of cumulated or fused colloidal particles. When colloidosomes are used for in situ encapsulation, it is still a challenge to achieve a high encapsulation efficiency and controllable release by an effective fabrication method. Herein, we present a highly efficient route for the large-scale preparation of colloidosomes. The biodegradable polylactic acid (PLA) nanoparticles (NPs) as shell materials can be synthesized using an antisolvent precipitation method, and the possible formation mechanism was given through the molecular dynamics (MD) simulation. The theoretical values are basically consistent with the experimental results. Through the use of the modified and unmodified PLA NPs, the colloidosomes with controllable shell porosities can be easily constructed using spray drying technology. We also investigate the mechanism of colloidosomes successfully self-assembled by PLA NPs with various factors of inlet temperature, feed rate, and flow rates of compressed air. Furthermore, avermectin (AVM) was used as a model for in situ encapsulation and a controllable release. The spherical modified colloidosomes encapsulating AVM not only achieve a small mean diameter of 1.57 µm but also realize a high encapsulation efficiency of 89.7% and impermeability, which can be further verified by the MD simulation. AVM molecules gather around and clog the shell pores during the evaporation of water molecules. More importantly, the PLA colloidosomes also reveal excellent UV-shielding properties, which can protect AVM from photodegradation.

Single-shot digital optical fluorescence phase conjugation through forward multiple-scattering samples.

Aberrations and multiple scattering in biological tissues critically distort light beams into highly complex speckle patterns. In this regard, digital optical phase conjugation (DOPC) is a promising technique enabling in-depth focusing. However, DOPC becomes challenging when using fluorescent guide stars for four main reasons: the low photon budget available, the large spectral bandwidth of the fluorescent signal, the Stokes shift between the emission and the excitation wavelength, and the absence of reference beam preventing holographic measurement. Here, we demonstrate the possibility to focus a laser beam through multiple-scattering samples by measuring speckle fields in a single acquisition step with a reference-free, high-resolution wavefront sensor. By taking advantage of the large spectral bandwidth of forward multiply scattering samples, digital fluorescence phase conjugation is achieved to focus a laser beam at the excitation wavelength while measuring the broadband speckle field arising from a micrometer-sized fluorescent bead.

A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis.

Tumor-associated macrophages (TAMs) are highly infiltrated in the tumor microenvironment (TME) of colorectal cancer (CRC) and play a vital role in CRC's development as well as prognosis. The required data were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas. Univariate Cox regression and least absolute shrinkage operator analyses were executed for model construction. TME assessment and immune prediction were performed using the ESTIMATE software package and the single sample genome enrichment analysis algorithm. The results show patients with low a TAMs risk score (TRS) had a better prognosis in both The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Patients with low TRS were more sensitive to 3 chemotherapeutic agents: oxaliplatin, paclitaxel, and cisplatin ( P <0.05). TME assessment showed that the low TRS group had less infiltration of M2 macrophages and regulatory T cells, but CD4 + T cells, NK cells, and dendritic cells occupy a greater proportion of TME. Low TRS group patients have a low StromalScore and ImmuneScore but have high TumorPurity. The immune checkpoint TIM-3 gene HAVCR2 expression was significantly higher in the high TRS group. Finally, we created a nomogram including TRS for forecasting survival, and TRS was significantly associated with the clinical stage of the patients. In conclusion, the TRS serves as a reliable prognostic indicator of CRC; it predicts patient outcomes to immunotherapy and chemotherapy and provides genomic evidence for the subsequent development of modulated TAMs for treating CRC.

BaSO4-Epoxy Resin Composite Film for Efficient Daytime Radiative Cooling.

Conventional cooling methods are based on active cooling technology by air conditioning, which consumes a large amount of energy and emits greenhouse gases. Radiative cooling is a novel promising passive cooling technology that uses external space as the cooling source and requires no additional energy consumption. Herein, we propose an approach to prepare highly dispersed BaSO4 nanoparticles (NPs) using a direct precipitation method combined with the in situ surface modification technology. The as-prepared PVP-modified BaSO4 NPs with an average size of 20 nm can be stably dispersed in ethanol for more than 6 months and then were used as building blocks to prepare spherical BaSO4 clusters with an average size of 0.9 µm using a scalable spray drying technique. The BaSO4 NPs/clusters (mass ratio 1:1) were used for preparing radiative cooling epoxy resin film, showing a high solar reflectance of 71% and a high sky window emissivity of 0.94. More importantly, this composite film displays superior radiative cooling performance, which can reduce the ambient temperature by 13.5 °C for the indoor test and 7 °C for the outdoor test. Compared with the commercial BaSO4 filled film, our BaSO4-epoxy resin composite film offers advantages not only in radiative cooling but also in mechanical properties with a 16.6% increase of tensile strength and 40.1% increase of elongation at break, demonstrating its great application potential in the field of building air conditioning.

Multi-target automatic positioning based on angle and distance parallel measurement.

Precisely and efficiently measuring three-dimensional coordinates of key points on large-scale components in the manufacturing process of aircraft and ships is critically essential. This study presents a multi-target automatic positioning method based on rapid angle and distance measurement in parallel. The measurement processes for angles and distances are decoupled and, when executed simultaneously, aims to enhance the measurement efficiency and automation compared with conventional metrology systems. A cooperative target is devised to realize the rotary-laser scanning angle measurement and absolute distance measurement in parallel. The method of multi-target rough positioning based on rotary-laser scanning and then the precise coordinate measurement method introducing absolute distance constraint are detailed. Especially for the distance measurement, we propose a method to determine the internal zero length and compensate for the distance error caused by mirror offset. A real-site experiment is implemented to verify the method's feasibility and demonstrate that the 3D coordinate measurement accuracy is better than 0.17 mm compared with laser tracker.

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis.

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities. In the reaction, three chemical bonds, including C═O, C─C, and C─H, are formed, providing a de novo synthesis reaction for chiral α,α-diarylketones. Moreover, this protocol provides a convenient and practical method to synthesize or modify complex bioactive molecules, including efficient routes to florylpicoxamid and BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, and the substituents of Hantzsch ester all play crucial roles in the stereocontrol of the reaction.

Schisandrin B inhibits tumor progression of hepatocellular carcinoma by targeting the RhoA/ROCK1 pathway.

Background: Schisandrin B (Sch. B) performs various pharmacological properties, including anticancer activities. However, the pharmacological mechanisms of Sch. B in hepatocellular carcinoma (HCC) are not fully elucidated. We investigated the impact and mechanism on progression in HCC, and to provide new experimental evidence for HCC treatment. Methods: To determine the inhibitory effect of Sch. B on HCC in vivo, 32 Balb/c nude mice were used to prepare the tumor-bearing mice model by subcutaneously inoculating HCC cells (Huh-7). As tumor volume grew to 100 mm3, mice were randomly divided into Saline (control group), 100 mg/kg Sch. B group (Sch. B-L), 200 mg/kg Sch. B group (Sch. B-M), and 400 mg/kg Sch. B group (Sch. B-H) (n=8). Saline or different concentration Sch. B was used to treat mice via gavage administration for 21 days. After mice were euthanized, tumor weight and volume were evaluated. Cell apoptosis was detected by TUNEL. Ki-67 and PCNA were detected by immunohistochemical staining. The RhoA and Rho-associated protein kinase 1 (ROCK1) were determined by western blot. In vitro experiment, Huh-7 cell were treated by Sch. B at 40, 30, 20, 10, 5, 1, and 0 µM to detect cell proliferation by Cell Counting Kit-8 (CCK-8). Huh-7 cells were divided as a control group, Sch. B group, and Sch. B + RhoA overexpression (Sch. B + RhoA) group. RhoA and ROCK1 were examined. The colony formation assay and flow cytometry were used to detect cell proliferation and apoptosis. The wound healing and Transwell assays were used for cell metastasis detection. Results: Our results showed 100, 200 and 400 mg/kg Sch. B significantly reduced tumor weight and volume. And 200 and 400 mg/kg Sch. B increased apoptosis, and reduced Ki-67 and PCNA levels, inhibited the RhoA and ROCK1 in vivo (P<0.05). In vitro experiment, Sch. B inhibited Huh-7 cell proliferation at concentration more than 10 µM (P<0.05). Sch. B decreased cell duplication, promoted apoptosis and blocked migration and invasion of Huh-7 (P<0.05). Sch. B inhibited RhoA and ROCK1 level as compared with control group (P<0.05). RhoA overexpression reversed the effect of Sch. B (P<0.05). Conclusions: Sch. B inhibits Huh-7 cells progression via RhoA/ROCK1 pathway. The results provide new evidence for the clinical treatment of HCC.

Hair follicle mesenchymal stem cell exosomal lncRNA H19 inhibited NLRP3 pyroptosis to promote diabetic mouse skin wound healing.

Skin wounds caused by diabetes are a major medical problem. Mesenchymal stem cell-derived exosomes hold promise to quicken wound healing due to their ability to transfer certain molecules to target cells, including mRNAs, microRNAs, lncRNAs, and proteins. Nonetheless, the specific mechanisms underlying this impact are not elucidated. Therefore, this research aimed to investigate the effect of MSC-derived exosomes comprising long non-coding RNA (lncRNA) H19 on diabetic skin wound healing. Hair follicle mesenchymal stem cells (HF-MSCs) were effectively isolated and detected, and exosomes (Exo) were also isolated smoothly. Pretreatment with 30 mM glucose for 24 h (HG) could efficiently induce pyroptosis in HaCaT cells. Exosomal H19 enhanced HaCaT proliferation and migration and inhibited pyroptosis by reversing the stimulation of the NLRP3 inflammasome. Injection of exosomes overexpressing lncRNA H19 to diabetic skin wound promoted sustained skin wound healing, whereas sh-H19 exosomes did not have this effect. In conclusion, Exosomes overexpressing H19 promoted HaCaT proliferation, migration and suppressed pyroptosis both in vitro and in vivo. Therefore, HFMSC-derived exosomes that overexpress H19 may be included in strategies for healing diabetic skin wounds.

Bismuth(III)-Catalyzed 1,8-Addition/Cyclization/Rearrangement of Propargylic para-Quinone Methides with 2-Vinylphenol: Synthesis of Indeno[2,1-c]chromenes.

The unique reactivity of in situ generated propargylic para-quinone methides as a new type of five-carbon synthon has been discovered by a novel bismuth(III)-catalyzed tandem annulation reaction. This 1,8-addition/cyclization/rearrangement cyclization cascade reaction is characterized by unusual structural reconstruction of 2-vinylphenol, involving cleavage of the C1'═C2' bond and formation of four new bonds. This method provides a convenient and mild approach to generate synthetically important functionalized indeno[2,1-c]chromenes. The mechanism of the reaction is proposed from several control experiments.

Single-nucleotide polymorphisms of TLR4 and GAS7 linked to primary open-angle glaucoma among patients of Shenyang, China.

The potential for adverse outcomes and classifications of glaucoma differ among race, country, gender, and family medical history. Nearly, 50 represent candidate genes are considered as potential contributors to the happening for the primary open-angle glaucoma (POAG) since the advent of GWASs. Our investigation is the first to report the Toll-like receptor 4 (TLR4) and growth arrest-specific 7 (GAS7) among people in Shenyang, China; to investigate whether single-nucleotide polymorphisms (SNPs) in (TLR4) or GAS7 gene are risk factors for POAG among people in Shenyang, China; and also to explore their potential pathogenic mechanisms. POAG patients from July 2015 to June 2019 at Shenyang Fourth People's Hospital were selected. A total of 218 POAG patients and 252 controls were enrolled. Eight potentially functional SNPs of TLR4 (rs7868859, rs7873784, rs77358523, and rs752998) and GAS7 (rs8012311, rs11656696, rs74629981, and rs9900085) were genotyped. Multifactor analysis was conducted to evaluate the correlation between TLR4, GAS7, and POAG. The allele frequency of rs7873784 of TLR4 demonstrated that the GC (P = 0.030), CC (P = 0.040), and GC + CC genotypes (P = 0.009) were significantly higher compared with CC genotype for POAG patients than that for controls. The rs8072311 and rs9900085 of GAS7 gene also were significantly associated with POAG. Haplotype analysis found that the C-A-T-A haplotype (order: rs7873784-rs77358523-rs752998-rs7868859) of TLR4 gene and the two haplotypes A-C-C-A and C-C-A-C of GAS7 (order: rs9900085-rs74629981-rs8072311-rs11656696) were associated with an elevated susceptibility to POAG (P < 0.05). In this study, rs7868859 of TLR4 and rs8012311 and rs9900085 polymorphisms of GAS7 were first identified to be related to POAG among people in Shenyang, China.

Day and night continuous high-resolution shallow-water depth detection with single-photon underwater lidar.

Single-photon lidar has emerged as a strong technology for bathymetric measurements. However, its heightened sensitivity additionally makes it susceptible to solar radiation noise, particularly in the green light wavelength where solar radiation is strong, posing challenges for its daytime operation. To address this issue, a single-photon underwater lidar system is proposed and demonstrated. This scheme has these features. 1) Underwater applications not only mitigate the impact of the air-water interface on laser transmission but also significantly attenuate solar radiation reaching the lidar due to the absorption and scattering properties of water. 2) The telescope is designed with a small aperture and narrow field of view to significantly suppress solar radiation. 3) A combination of a narrowband laser and narrowband filter technique is effectively employed to minimize residual solar radiation, thus enabling continuous bathymetric observation capabilities during both day and night. 4) After acquiring the backscattered signal from the bottom, a water depth extraction algorithm utilizing bi-Gaussian fitting is proposed. To demonstrate the robustness of the lidar and the effectiveness of the algorithm, the underwater single-photon lidar system is deployed on a ship to conduct cruise surveys of two bays in the nearshore area, as well as a full-day stationary observation experiment. The lidar measurements are highly consistent with the synchronized sonar observations. The full-day stationary observation experiment showcased its capability to deliver continuous measurements throughout the day and night. These results demonstrate the potential of the system in various applications, including high-precision underwater terrain mapping, obstacle avoidance for underwater platforms, and underwater target imaging.

3D nanoparticle superlocalization with a thin diffuser.

We report on the use of a thin diffuser placed in the close vicinity of a camera sensor as a simple and effective way to superlocalize plasmonic nanoparticles in 3D. This method is based on holographic reconstruction via quantitative phase and intensity measurements of a light field after its interaction with nanoparticles. We experimentally demonstrate that this thin diffuser can be used as a simple add-on to a standard bright-field microscope to allow the localization of 100 nm gold nanoparticles at video rate with nanometer precision (1.3 nm laterally and 6.3 nm longitudinally). We exemplify the approach by revealing the dynamic Brownian trajectory of a gold nanoparticle trapped in various pockets within an agarose gel. The proposed method provides a simple but highly performant way to track nanoparticles in 3D.

Effects of Qidantang Granule on early stage of diabetic kidney disease in rats.

Diabetic kidney disease (DKD), is one of the most common vascular diseases caused by diabetes, eventually progressing into glomerular sclerosis. Qidantang Granule is a traditional Chinese medicine that is commonly used for DKD. However, there is still no experimental evidence for its effectiveness on DKD. 8-week-old Sprague Dawley male rats were fed on high-fat and high-sugar diet for 4 weeks, and then intraperitoneally injected with 35 mg/kg streptozotocin (STZ) to induce diabetes. Diabetic rats were randomly divided into three groups, and orally administrated with vehicle, 50 mg/kg or 200 mg/kg Qidantang Granule respectively, once daily for 9 weeks. Qidantang Granule effectively reduced food and water intake, body weight and fasting blood glucose, decreased inflammation and oxidative stress, ameliorated renal injury through suppressing PI3K signaling pathway in STZ-induced DKD rats. Our results provide experimental evidence to demonstrate the pharmacological mechanism of Qidantang Granule in the treatment of DKD.

Multi-objective optimisation for cell-level disassembly of waste power battery modules in human-machine hybrid mode.

The rapid global growth in the production of electric vehicles (EVs) will produce numerous waste power battery modules (WPBMs) in the future, which will create significant challenges concerning waste disposal. Therefore, measures to disassemble and recycle WPBMs before using them in other fixed scenarios provide an opportunity for research. First, considering battery components' hazards and complex properties, a human-machine collaborative cell-level disassembly model of WPBMs is proposed. Second, the WPBMs from the Tesla Model S are selected as the case study to verify reliability and validity. Finally, two different disassembly schemes are obtained by solving the proposed model using NSGA-II based on the actual data from resource-recycling companies. The results show that: 1) The proposed model and method can realize the cell-level disassembly of WPBMs and assign the disassembly tasks of hazard components to robots and the disassembly tasks of complex components to humans. 2) The two disassembly schemes obtained are two solutions that do not dominate each other, and the four objectives (number of workstations, workstation idle time, number of workers, and disassembly cost) are optimized simultaneously. 3) The proposed model can provide decision-makers with additional options when incorporating the number of workers into enterprise risk indicators.

Temporal and Spatial Distribution Analysis of Atmospheric Pollutants in Chengdu-Chongqing Twin-City Economic Circle.

In order to study the temporal and spatial distribution characteristics of atmospheric pollutants in cities (districts and counties) in the Chengdu-Chongqing Twin-city Economic Circle (CCEC) and to provide a theoretical basis for atmospheric pollution prevention and control, this paper combined Ambient Air Quality Standards (AAQS) and WHO Global Air Quality Guidelines (GAQG) to evaluate atmospheric pollution and used spatial correlation to determine key pollution areas. The results showed that the distribution of atmospheric pollutants in CCEC presents a certain law, which was consistent with the air pollution transmission channels. Except for particulate matter with an aerodynamic diameter equal to or less than 2.5 µm (PM2.5) and ozone (O3), other pollutants reached Grade II of AAQS in 2020, among which particulate matter with an aerodynamic diameter equal to or less than 10 µm (PM10), PM2.5, sulfur dioxide (SO2), nitrogen dioxide (NO2) and carbon monoxide (CO) have improved. Compared with the air quality guidelines given in the GAQG, PM10, PM2.5, NO2 and O3 have certain effects on human health. The spatial aggregation of PM10 and PM2.5 decreased year by year, while the spatial aggregation of O3 increased with the change in time, and the distribution of NO2 pollution had no obvious aggregation. Comprehensive analysis showed that the pollution problems of particulate matter, NO2 and O3 in CCEC need to be further controlled.

Local Surface Chemistry Dynamically Monitored by Quantitative Phase Microscopy.

Surface modification by photo grafting constitutes an interesting strategy to prepare functional surfaces. Precision applications, however, demand quantitative methods able to monitor and control the amount and distribution of surface modifications, which is hard to achieve, particularly in operando conditions. In this paper, a label-free, cost-effective, all-optical method based on wavefront sensing which is able to quantitatively track the evolution of grafted layers in real-time, is presented. By positioning a simple thin diffuser in the close vicinity of a camera, the thickness of grafted patterns is directly evaluated with sub-nanometric sensitivity and diffraction-limited lateral resolution. By performing an in-depth kinetic analysis of the local modification of an inert substrate (glass cover slips) through photografting of arydiazonium salts, different growth regimes are characterized and several parameters are estimated, such as the grafting efficiency, density and the apparent refractive index distribution of the resulting grafted layers. Both focused and widefield-grafting can be quantitatively monitored in real time, providing valuable guidelines to maximize functionalization efficiency. The association of a well-characterized versatile photografting reaction with the proposed flexible and sensitive monitoring strategy enables functional surfaces to be prepared, and puts surface micro- to submicro-structuration within the reach of most laboratories.

Photon-counting distributed free-space spectroscopy.

Spectroscopy is a well-established nonintrusive tool that has played an important role in identifying and quantifying substances, from quantum descriptions to chemical and biomedical diagnostics. Challenges exist in accurate spectrum analysis in free space, which hinders us from understanding the composition of multiple gases and the chemical processes in the atmosphere. A photon-counting distributed free-space spectroscopy is proposed and demonstrated using lidar technique, incorporating a comb-referenced frequency-scanning laser and a superconducting nanowire single-photon detector. It is suitable for remote spectrum analysis with a range resolution over a wide band. As an example, a continuous field experiment is carried out over 72 h to obtain the spectra of carbon dioxide (CO2) and semi-heavy water (HDO, isotopic water vapor) in 6 km, with a range resolution of 60 m and a time resolution of 10 min. Compared to the methods that obtain only column-integrated spectra over kilometer-scale, the range resolution is improved by 2-3 orders of magnitude in this work. The CO2 and HDO concentrations are retrieved from the spectra acquired with uncertainties as low as ±1.2% and ±14.3%, respectively. This method holds much promise for increasing knowledge of atmospheric environment and chemistry researches, especially in terms of the evolution of complex molecular spectra in open areas.