Multiple Human Population Movements and Cultural Dispersal Events Shaped the Landscape of Chinese Paternal Heritage.

Large-scale genomic projects and ancient DNA innovations have ushered in a new paradigm for exploring human evolutionary history. However, the genetic legacy of spatiotemporally diverse ancient Eurasians within Chinese paternal lineages remains unresolved. Here, we report an integrated Y-chromosome genomic database encompassing 15,563 individuals from both modern and ancient Eurasians, including 919 newly reported individuals, to investigate the Chinese paternal genomic diversity. The high-resolution, time-stamped phylogeny reveals multiple diversification events and extensive expansions in the early and middle Neolithic. We identify four major ancient population movements, each associated with technological innovations that have shaped the Chinese paternal landscape. First, the expansion of early East Asians and millet farmers from the Yellow River Basin predominantly carrying O2/D subclades significantly influenced the formation of the Sino-Tibetan people and facilitated the permanent settlement of the Tibetan Plateau. Second, the dispersal of rice farmers from the Yangtze River Valley carrying O1 and certain O2 sublineages reshapes the genetic makeup of southern Han Chinese, as well as the Tai-Kadai, Austronesian, Hmong-Mien, and Austroasiatic people. Third, the Neolithic Siberian Q/C paternal lineages originated and proliferated among hunter-gatherers on the Mongolian Plateau and the Amur River Basin, leaving a significant imprint on the gene pools of northern China. Fourth, the J/G/R paternal lineages derived from western Eurasia, which were initially spread by Yamnaya-related steppe pastoralists, maintain their presence primarily in northwestern China. Overall, our research provides comprehensive genetic evidence elucidating the significant impact of interactions with culturally distinct ancient Eurasians on the patterns of paternal diversity in modern Chinese populations.

Genetic history and biological adaptive landscape of the Tujia people inferred from shared haplotypes and alleles.

BACKGROUND: High-quality genomic datasets from under-representative populations are essential for population genetic analysis and medical relevance. Although the Tujia are the most populous ethnic minority in southwestern China, previous genetic studies have been fragmented and only partially reveal their genetic diversity landscape. The understanding of their fine-scale genetic structure and potentially differentiated biological adaptive features remains nascent. OBJECTIVES: This study aims to explore the demographic history and genetic architecture related to the natural selection of the Tujia people, focusing on a meta-Tujia population from the central regions of the Yangtze River Basin. RESULTS: Population genetic analyses conducted on the meta-Tujia people indicate that they occupy an intermediate position in the East Asian North-South genetic cline. A close genetic affinity was identified between the Tujia people and neighboring Sinitic-speaking populations. Admixture models suggest that the Tujia can be modeled as a mixture of northern and southern ancestries. Estimates of f3/f4 statistics confirmed the presence of ancestral links to ancient Yellow River Basin millet farmers and the BaBanQinCen-related groups. Furthermore, population-specific natural selection signatures were explored, revealing highly differentiated functional variants between the Tujia and southern indigenous populations, including genes associated with hair morphology (e.g., EDAR) and skin pigmentation (e.g., SLC24A5). Additionally, both shared and unique selection signatures were identified among ethnically diverse but geographically adjacent populations, highlighting their extensive admixture and the biological adaptations introduced by this admixture. CONCLUSIONS: The study unveils significant population movements and genetic admixture among the Tujia and other ethno-linguistically diverse East Asian groups, elucidating the differentiated adaptation processes across geographically diverse populations from the current genetic landscape.

Population genetic admixture and evolutionary history in the Shandong Peninsula inferred from integrative modern and ancient genomic resources.

BACKGROUND: Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of ethnolinguistically diverse populations in modern China and the entire landscape of deep genetic structure and variation discovery in modern East Asians. However, the direct links between ANEA and geographically proximate modern populations, as well as the biological adaptive processes involved, remain poorly understood. RESULTS: Here, we generated genome-wide SNP data for 264 individuals from geographically different Han populations in Shandong. An integrated genomic resource encompassing both modern and ancient East Asians was compiled to examine fine-scale population admixture scenarios and adaptive traits. The reconstruction of demographic history and hierarchical clustering patterns revealed that individuals from the Shandong Peninsula share a close genetic affinity with ANEA, indicating long-term genetic continuity and mobility in the lower Yellow River basin since the early Neolithic period. Biological adaptive signatures, including those related to immune and metabolic pathways, were identified through analyses of haplotype homozygosity and allele frequency spectra. These signatures are linked to complex traits such as height and body mass index, which may be associated with adaptations to cold environments, dietary practices, and pathogen exposure. Additionally, allele frequency trajectories over time and a haplotype network of two highly differentiated genes, ABCC11 and SLC10A1, were delineated. These genes, which are associated with axillary odor and bilirubin metabolism, respectively, illustrate how local adaptations can influence the diversification of traits in East Asians. CONCLUSIONS: Our findings provide a comprehensive genomic dataset that elucidates the fine-scale genetic history and evolutionary trajectory of natural selection signals and disease susceptibility in Han Chinese populations. This study serves as a paradigm for integrating spatiotemporally diverse ancient genomes in the era of population genomic medicine.

Probing the Alcoholysis Degree of Polyvinyl Alcohol by Synergistic Coordination-Regulated Fluorescence.

Polyvinyl alcohol (PVA) with abundant hydroxyl groups (-OH) has been widely used for membranes, hydrogels, and films, and its function is largely affected by the alcoholysis degree. Therefore, the development of rapid and accurate methods for alcoholysis degree determination in PVAs is important. In this contribution, we have proposed a novel fluorescence-based platform for probing the alcoholysis degree of PVA by using the (E)-N-(4-methoxyphenyl)-1-(quinolin-2-yl)methanimine (QPM)-Zn2+ complex as the reporter. The mechanism study disclosed that the strong coordination between -OH and Zn2+ induced the capture of the QPM-Zn2+ complex and promoted its subsequent immobilization into the noncrystalline area. The immobilization of the QPM-Zn2+ complex restricted its molecular rotation and reduced the nonirradiative transition, thus yielding bright emissions. In addition, the practical applications of this proposed method were further validated by the accurate alcoholysis degree determination of blind PVA samples with the confirmation of the National Standard protocol. It is expected that the developed fluorescence approach in this work might become an admissive strategy for screening the alcoholysis degree of PVA.

Manipulation and applications of ultrafast all-optical switching based on transient absorption and dispersion in KTN crystals.

Potassium tantalate niobate (KTN) represents a noteworthy category of optical crystals known for their superior nonlinear optical properties. In this study, we conducted measurements of femtosecond time-resolved transient absorption (TA) spectra in KTa0.57Nb0.43O3 crystals. Notably, a rapid and pronounced "plateau" phase, ∼1.5 ps in duration, was detected at the onset of the TA kinetics and succeeded by two distinct decay components, exhibiting lifetimes of ∼140 ps and over 10 ns, respectively. We attribute these observations to a decay process involving two-photon absorption, dispersion characteristics, and excited state absorption. Based on this unique TA characteristic of KTN crystals, an all-optical switching strategy was proposed and utilized to measure the ultrafast lasing dynamics of single-crystal CH3NH3PbBr3 nanowires. This polarization-independent TA gate approach offers an adjustable gate width combining ps and ns time scales and introduces a versatile tool for advanced optical applications.

Longitudinal metabolomics of human plasma reveal metabolic dynamics and predictive markers of antituberculosis drug-induced liver injury.

Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.

SCAPE: a mixture model revealing single-cell polyadenylation diversity and cellular dynamics during cell differentiation and reprogramming.

Alternative polyadenylation increases transcript diversities at the 3' end, regulating biological processes including cell differentiation, embryonic development and cancer progression. Here, we present a Bayesian method SCAPE, which enables de novo identification and quantification of polyadenylation (pA) sites at single-cell level by utilizing insert size information. We demonstrated its accuracy and robustness and identified 31 558 sites from 36 mouse organs, 43.8% (13 807) of which were novel. We illustrated that APA isoforms were associated with miRNAs binding and regulated in tissue-, cell type-and tumor-specific manners where no difference was found at gene expression level, providing an extra layer of information for cell clustering. Furthermore, we found genome-wide dynamic changes of APA usage during erythropoiesis and induced pluripotent stem cell (iPSC) differentiation, suggesting APA contributes to the functional flexibility and diversity of single cells. We expect SCAPE to aid the analyses of cellular dynamics and diversities in health and disease.

Fluoride-activated photothermal system for promoting bacteria-infected wound healing.

Although photothermal therapy (PTT) employing nanozymes has shown excellent antibacterial potential, excessive heating generally harms host cells and hinders recovery. Herein, we report an innovative technique for acquiring the programmed temperature by managing the catalytic activity of nanozymes. The photothermal system of CeO2 + F- + TMB can obtain precise photothermal temperature by adjusting the concentration of fluoride ions under near-infrared irradiation. At the optimized photothermal temperature, the photothermal system affords fine photothermal antibacterial treatment with high-efficiency antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro. In vivo wound healing experiments confirm that the system can effectively promote fibroblast proliferation, angiogenesis and collagen deposition with remarkable wound healing efficiency. This strategy offers a novel design concept for creating a new generation of PTT and opens the way for the creation of alternative antibiotics.

Identifying Performance Descriptors in CO2 Hydrogenation over Iron-Based Catalysts Promoted with Alkali Metals.

Alkali metal promoters have been widely employed for preparation of heterogeneous catalysts used in many industrially important reactions. However, the fundamentals of their effects are usually difficult to access. Herein, we unravel mechanistic and kinetic aspects of the role of alkali metals in CO2 hydrogenation over Fe-based catalysts through state-of-the-art characterization techniques, spatially resolved steady-state and transient kinetic analyses. The promoters affect electronic properties of iron in iron carbides. These carbide characteristics determine catalyst ability to activate H2 , CO and CO2 . The Allen scale electronegativity of alkali metal promoter was successfully correlated with the rates of CO2 hydrogenation to higher hydrocarbons and CH4 as well as with the rate constants of individual steps of CO or CO2 activation. The derived knowledge can be valuable for designing and preparing catalysts applied in other reactions where such promoters are also used.

Extraordinary transmission in an add-drop filter configuration driven by nonconservative coupling.

We proposed a nonconservative coupling scheme based on the add-drop filter configuration, in which a high Q factor passive microtoroid resonator is indirectly driven by an active unit, thus providing an additional coupling which might be comparable to a mode decay rate. Extraordinary scattering points are predicted when one of the supermodes becomes lossless. Specifically, when the inherent coupling strength is set at half of the mode's total decay rate, controllable transmission peaks can be realized by tuning the nonconservative coupling strength and phase delay. Our theoretic research might find potential application in tunable light steering based on non-Hermitian resonator systems.

Highly undersampled magnetic resonance imaging reconstruction using autoencoding priors.

PURPOSE: Although recent deep learning methodologies have shown promising results in fast MR imaging, how to explore it to learn an explicit prior and leverage it into the observation constraint is still desired. METHODS: A denoising autoencoder (DAE) network is leveraged as an explicit prior to address the highly undersampling MR image reconstruction problem. First, inspired by the observation that the prior information learned from high-dimension signals is more effective than that from the low-dimension counterpart in image restoration tasks, we train the network in a multichannel scenario and apply the learned network to single-channel image reconstruction by a variables augmentation technique. Second, because of the fact that multiple implementations of artificial noise generation in DAE favors a better underlying result, we introduce a 2-sigma rule to complement each other for improving the final reconstruction. The whole algorithm is tackled by proximal gradient descent. RESULTS: Experimental results under varying sampling trajectories and acceleration factors consistently demonstrate the superiority of the enhanced autoencoding priors, in terms of peak signal-to-noise ratio, structural similarity, and high-frequency error norm. CONCLUSION: A simple and effective way to incorporate the DAE prior into highly undersampling MR reconstruction is proposed. Once the DAE prior is obtained, it can be applied to the reconstruction tasks with different sampling trajectories and acceleration factors, and achieves superior performance in comparison with state-of-the-art methods.

Effect of phosphate on the adsorption of antibiotics onto iron oxide minerals: Comparison between tetracycline and ciprofloxacin.

With the broadly application of antibiotics to treat infectious diseases in humans and animals, antibiotic contaminants such as tetracycline (TC) and ciprofloxacin (CIP) have been detected in soil environments, where iron oxide minerals and phosphate are ubiquitous. To date, the influence of phosphate on the adsorption behaviors of TC/CIP onto iron oxides is still poorly understood. In this study, the effects of phosphate on the adsorptions of TC and CIP onto iron oxide minerals were investigated. Adsorption isotherms showed that the adsorption affinities of TC and CIP onto the three iron oxide minerals were in the order of goethite > hematite > magnetite with or without phosphate, the trend was dominated by different surface area and amount of surface hydroxyl groups of iron oxide minerals. Meanwhile, TC contains more functional groups than CIP for bonding, which resulted in greater adsorption affinity of three iron oxides to TC than that to CIP. Interestingly, phosphate weakened TC adsorption, while enhanced CIP adsorption, on the three iron oxides. This observation was ascribed to that phosphate anion enhanced the surface negative charge of iron oxides, which reinforced the electrostatic repulsion between iron oxides and negatively charged TC, also reinforced the electrostatic attraction between iron oxides and positively charged CIP. Furthermore, the inhibitory effect of phosphate on TC adsorption was dramatically enhanced at high pH, while the promoting effect of phosphate on CIP adsorption was slightly changed with various pH. Our results highlight the importance of phosphate in exploring the environmental fate of antibiotics in natural environment.

Pulegone inhibits inflammation via suppression of NLRP3 inflammasome and reducing cytokine production in mice.

Context: Pulegone, a key compound in Schizonepeta essential oil, has been identified as an anti-inflammatory. However, its underlying molecular mechanisms on NLR family pyrin domain containing 3 (NLRP3) inflammasome have not been elucidated. Objective: Here, the modulatory effects of pulegone on NLRP3 inflammasome were investigated. Materials and methods: The C57BL/6J mice were randomly divided into five groups: Normal, Lipopolysaccharides (LPS), Dexamethasone (DEX, 5 mg/kg), Pulegone (0.095 and 0.190 g/kg) groups. All mice were challenged by LPS except for the Normal group. Results: A reduced expression of Interleukin-18 (IL-18), Interleukin-1ß (IL-1ß), Interleukin-5 (IL-5), Tumor necrosis factor-α (TNF-α), Interferon-gamma (IFN-γ), Monocyte chemoattratctant protein-1 (MCP-1), Macrophage inflammatory protein-1ß (MIP-1ß), Monocyte colony stimulating factor (M-CSF) and Granulocyte-macrophage colony stimulating factor (GM-CSF) in serum were detected in the pulegone groups as compared to the LPS group. In addition, a reduced mRNA and protein expression production of ASC, NLRP3, and Caspase-1 were detected in lungs after pulegone administration. Histological analysis results indicated that the histological changes of lungs caused by LPS were ameliorated by pulegone. Immunohistochemical study showed a decreased positive cell numbers of P2X7R in Pulegone (0.095 and 0.190 g/kg) groups. Conclusion: Pulegone exerts anti-inflammatory effects on LPS-induced sepsis mice via inhibition of the NLRP3 expression.

[Molecular mechanism of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair against sepsis based on integrative pharmacology platform of traditional Chinese medicine].

Guizhi Decoction is a resolving agent,which is a classic prescription for traditional Chinese medicine. It is effective in the treatment of sepsis in clinical practice. However,due to the complexity of the prescription,its anti-sepsis mechanism is difficult to be clarified. The " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair,as the classic compatibility for medicinal and medicinal herbs,is the core of Guizhi Decoction. In this study,Cinnamomi Ramulus-Paeoniae Radix Alba drug pair was used as the research object and the molecular mechanism of its treatment of sepsis was investigated by analyzing the chemical compositions with integrative pharmacology platform( TCMIP,http://www.tcmip.cn/),predicting disease target,analyzing gene function and pathway of " Cinnamomi Ramulus-Paeoniae Radix Alba" in treatment of sepsis,and establishing a multi-dimensional network relationship of " Chinese medicine-chemical components-core targets-key pathways". The prediction results of " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair showed that its anti-sepsis effect was associated with 45 active components,and the active components played an anti-sepsis role through multiple targets and pathways,involving inflammatory targets such as PF4,MyD88,TLR4,BDKRB2,CD14,and NOS3. The sepsis was relieved mainly by regulating Toll like signaling pathway,Fox O signaling pathway,chemokines signaling pathway,thyroid and insulin endocrine signaling pathways and biological processes. This study provides a scientific basis for further development of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair and Guizhi Decoction against sepsis.

Anti-sepsis effect of Xiaochaihu decoction based on the TLR4/MyD88/NF-κB signalling pathway.

The aims of this study were to explore the protective effect of Xiaochaihu decoction in mice with sepsis induced by intraperitoneal injection; to explore its anti-inflammatory effect on the TLR4-MyD88-NF-κB signalling pathway; and to explore the main material basis of the anti-inflammatory effect of Xiaochaihu decoction, with the aim of supplementing and expanding the associated research and providing a scientific foundation for the clinical use of the decoction. The effects of Xiaochaihu decoction on septic mice were analysed by measurements of white blood cells (WBC) and Platelets (PLT); Nitric Oxide (NO) level in serum; IL-6, IL-1ß and TNF-α levels in serum; RT-PCR; Haematoxylin-Eosin (HE) immunohistochemistry; western blotting (WB). The results showed the excellent in vivo anti-inflammatory effects of Xiaochaihu decoction in LPS-induced septic mice, through down regulation of the gene and protein expression of TLR4, MYD88, TRAF6, IKK, IKBα and p65 and the subsequent reduction in the release of inflammatory mediators IL-6, IL-1ß, TNF-α and NO. Moreover, significant anti-septic effect was observed from high and medium doses of Xiaochaihu decoction, but not from the low dose.

A machine learning-based predictive model of causality in orthopaedic medical malpractice cases in China.

PURPOSE: To explore the feasibility and validity of machine learning models in determining causality in medical malpractice cases and to try to increase the scientificity and reliability of identification opinions. METHODS: We collected 13,245 written judgments from PKULAW.COM, a public database. 963 cases were included after the initial screening. 21 medical and ten patient factors were selected as characteristic variables by summarising previous literature and cases. Random Forest, eXtreme Gradient Boosting (XGBoost) and Light Gradient Boosting Machine (LightGBM) were used to establish prediction models of causality for the two data sets, respectively. Finally, the optimal model is obtained by hyperparameter tuning of the six models. RESULTS: We built three real data set models and three virtual data set models by three algorithms, and their confusion matrices differed. XGBoost performed best in the real data set, with a model accuracy of 66%. In the virtual data set, the performance of XGBoost and LightGBM was basically the same, and the model accuracy rate was 80%. The overall accuracy of external verification was 72.7%. CONCLUSIONS: The optimal model of this study is expected to predict the causality accurately.

Transport of sulfanilamide in saturated porous media under different solution chemistry conditions: role of physicochemical characteristics of soils.

Identification of the transport of sulfonamide antibiotics in soils facilitates a better understanding of the environmental fate and behaviors of these ubiquitous contaminants. In this study, the mobility properties of sulfanilamide (SNM, a typical sulfonamide antibiotic) through saturated soils with different physicochemical characteristics were investigated. The results showed that the physicochemical characteristics controlled SNM mobility. Generally, the mobility of SNM was positively correlated with CEC values and soil organic matter content, which was mainly related to the interactions between the organic matter in soils and SNM molecules via π-π stacking, H-bonding, ligand exchange, and hydrophobic interaction. Furthermore, higher clay mineral content and lower sand content were beneficial for restraining SNM transport in the soils. Unlike Na+, Cu2+ ions could act as bridging agents between the soil grains and SNM molecules, contributing to the relatively weak transport of SNM. Furthermore, the trend of SNM mobility in different soil columns was unaffected by solution pH (5.0-9.0). Meanwhile, for a given soil, the SNM mobility was promoted as the solution pH values increased, which was caused by the enhanced electrostatic repulsion between SNM- species and soil particles as well as the declined hydrophobic interaction between SNM and soil organic matter. The obtained results provide helpful information for the contribution of soil physicochemical characteristics to the transport behaviors of sulfonamide antibiotics in soil-water systems.

Dopamine-based selective spectrophotometry p-aminosalicylic acid assay by hydrolyzate-triggered formation of azamonardine-like products.

BACKGROUND: The selective recognition of drugs and its metabolism or decomposition products is significant to drug development and drug resistance research. Fluorescence-based techniques provide satisfying sensitivity by target-triggered chemical reaction. However, the interference from the matrix or additives usually restricts the specific detection. It is highly desirable to explore specific chemical reactions for achieving selective perception of these species. RESULTS: We report a specific m-aminophenol (MAP)-dopamine (DA) reaction, which generates highly fluorescent azamonardine-like products. Based on this reaction, fluorometric and indirect detection of p-aminosalicylic acid (typical antituberculosis drug, PAS) can be realized using the DA-based probe with high sensitivity. The acid induces the decarboxylation of PAS and produces MAP, which reacts with DA and generates fluorescent azamonardine-like products. The practical application of the proposed method is validated by the accurate PAS analysis in urine samples and Pasinazid tablets. Interestingly, none of additives in the Pasinazid tablets contribute comparable fluorescence variation. SIGNIFICANCE: This work discovers a new MAP-DA reaction for the first time, it not only explores sensitive PAS drug detection probe, but also demonstrates the feasibility of the development of novel drug analysis platform by recognizing decomposition product with specific reaction. Thus, new avenues for the exploration of simple and rapid spectrophotometric probes toward various drug analytes with high specify and sensitivity based on this tactic might be possible in analytical and drug-related fields.

Harmonic and DC Bias Hysteresis Characteristics Simulation Based on an Improved Preisach Model.

Transformers, reactors and other electrical equipment often work under harmonics and DC-bias working conditions. It is necessary to quickly and accurately simulate the hysteresis characteristics of soft magnetic materials under various excitation conditions in order to achieve accurate calculations of core loss and the optimal design of electrical equipment. Based on Preisach hysteresis model, a parameter identification method for asymmetric hysteresis loop simulation is designed and applied to the simulation of hysteresis characteristics under bias conditions of oriented silicon steel sheets. In this paper, the limiting hysteresis loops of oriented silicon steel sheets are obtained through experiments under different working conditions. The first-order reversal curves(FORCs) with asymmetric characteristics is generated numerically, and then the Everett function is established under different DC bias conditions. The hysteresis characteristics of the oriented silicon steel sheets under harmonics and DC bias are simulated by improving FORCs identification method of the Preisach model. By comparing the results of simulation and experiment, the effectiveness of the proposed method is verified, so as to provide an important reference for material production and application.

Efficacy and safety of novel carbapenem-ß-lactamase inhibitor combinations: imipenem-cilastatin/relebactam results from randomized controlled trials.

Background: Gram-negative bacteria is a global public health problem. Treatment options include novel beta-lactamase inhibitors. Objectives: The objective of this study was to collect information on the efficacy and safety of novel ß-lactamase inhibitor combinations such as imipenem-cilastatin/relebactam (IMI/REL). Methods: In order to comprehensively evaluate the clinical, microbiological, and adverse events outcomes, a meta-analysis was conducted on clinical trials comparing novel ß-lactamase inhibitor combinations with existing comparator therapies. Results: Four studies comprising 948 patients were included in the analysis. IMI/REL therapy demonstrated similar clinical responses to comparators across various treatment visits, including discontinuation of intravenously administered therapy visits [DCIV, RR = 1.00 (0.88, 1.12)], early follow-up visits [EFU, RR = 1.00 (0.89, 1.14)], late follow-up visits [LFU, RR = 1.00 (0.88, 1.13)]. Moreover, no significant difference in the microbiologic response of MITT patients was observed between IMI/REL and comparators across DCIV [RR = 0.99 (0.89, 1.11)], EFU [RR = 1.01 (0.95, 1.07)], and LFU visits [RR = 1.00 (90.94, 1.07)]. In terms of safety, therapy with IMI/REL and comparators exhibited similar risks of at least one adverse event (AE), drug-related AEs, and discontinuation due to AEs. The incidence of serious AEs (SAEs) was significantly lower in the IMI/REL group compared to the comparison groups. The predominant AEs were gastrointestinal disorders, with no significant difference observed between the IMI/REL group and comparators. Conclusion: The clinical and microbiologic response to IMI/REL in the treatment of bacterial infection was comparable to that of the comparator. Furthermore, the incidence of AEs and the tolerability of IMI/REL were similar among the comparators. Based on these findings, IMI/REL can be considered as a viable alternative treatment option.