The association and underlying mechanism of the digit ratio (2D:4D) in hypospadias.

ABSTRACT: The second-to-fourth digit (2D:4D) ratio is thought to be associated with prenatal androgen exposure. However, the relationship between the 2D:4D ratio and hypospadias is poorly understood, and its molecular mechanism is not clear. In this study, by analyzing the hand digit length of 142 boys with hypospadias (23 distal, 68 middle, and 51 proximal) and 196 controls enrolled in Shanghai Children's Hospital (Shanghai, China) from December 2020 to December 2021, we found that the 2D:4D ratio was significantly increased in boys with hypospadias (P < 0.001) and it was positively correlated with the severity of the hypospadias. This was further verified by the comparison of control mice and prenatal low testosterone mice model obtained by knocking out the risk gene (dynein axonemal heavy chain 8 [DNAH8]) associated with hypospadias. Furthermore, the discrepancy was mainly caused by a shift in 4D. Proteomic characterization of a mouse model validated that low testosterone levels during pregnancy can impair the growth and development of 4D. Comprehensive mechanistic explorations revealed that during the androgen-sensitive window, the downregulation of the androgen receptor (AR) caused by low testosterone levels, as well as the suppressed expression of chondrocyte proliferation-related genes such as Wnt family member 5a (Wnt5a), Wnt5b, Smad family member 2 (Smad2), and Smad3; mitochondrial function-related genes in cartilage such as AMP-activated protein kinase (AMPK) and nuclear respiratory factor 1 (Nrf-1); and vascular development-related genes such as myosin light chain (MLC), notch receptor 3 (Notch3), and sphingosine kinase 1 (Sphk1), are responsible for the limitation of 4D growth, which results in a higher 2D:4D ratio in boys with hypospadias via decreased endochondral ossification. This study indicates that the ratio of 2D:4D is a risk marker of hypospadias and provides a potential molecular mechanism.

Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

BACKGROUND: Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. METHODS: haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. RESULTS: The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at - 80°C, 3 months at - 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. CONCLUSION: haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

Biobased Inks Based on Cuttlefish Ink and Cellulose Nanofibers for Biodegradable Patterned Soft Actuators.

Soft actuators with stimuli-responsive and reversible deformations have shown great promise in soft robotics. However, some challenges remain in existing actuators, such as the materials involved derived from nonrenewable resources, complex and nonscalable preparation methods, and incapability of complex and programmable deformation. Here, a biobased ink based on cuttlefish ink nanoparticles (CINPs) and cellulose nanofibers (CNFs) was developed, allowing for the preparation of biodegradable patterned actuators by direct ink writing technology. The hybrid CNF/CINP ink displays good rheological properties, allowing it to be accurately printed on a variety of flexible substrates. A bilayer actuator was developed by printing an ink layer on a biodegradable poly(lactic acid) film using extrusion-based 3D printing technology, which exhibits reversible and large bending behavior under the stimuli of humidity and light. Furthermore, programmable and reversible folding and coiling deformations in response to stimuli have been achieved by adjusting the ink patterns. This work offers a fast, scalable, and cost-effective strategy for the development of biodegradable patterned actuators with programmable shape-morphing.

Guard cell and subsidiary cell sizes are key determinants for stomatal kinetics and drought adaptation in cereal crops.

Climate change-induced drought is a major threat to agriculture. C4 crops have a higher water use efficiency (WUE) and better adaptability to drought than C3 crops due to their smaller stomatal morphology and faster response. However, our understanding of stomatal behaviours in both C3 and C4 Poaceae crops is limited by knowledge gaps in physical traits of guard cell (GC) and subsidiary cell (SC). We employed infrared gas exchange analysis and a stomatal assay to explore the relationship between GC/SC sizes and stomatal kinetics across diverse drought conditions in two C3 (wheat and barley) and three C4 (maize, sorghum and foxtail millet) upland Poaceae crops. Through statistical analyses, we proposed a GCSC-τ model to demonstrate how morphological differences affect stomatal kinetics in C4 Poaceae crops. Our findings reveal that morphological variations specifically correlate with stomatal kinetics in C4 Poaceae crops, but not in C3 ones. Subsequent modelling and experimental validation provide further evidence that GC/SC sizes significantly impact stomatal kinetics, which affects stomatal responses to different drought conditions and thereby WUE in C4 Poaceae crops. These findings emphasize the crucial advantage of GC/SC morphological characteristics and stomatal kinetics for the drought adaptability of C4 Poaceae crops, highlighting their potential as future climate-resilient crops.

Chelativorans salis sp. nov., a slightly halophilic bacterium isolated from an enrichment system with saline lake sediment.

A Gram-stain-negative, non-motile, and slightly halophilic alphaproteobacterium, designated strain EGI FJ00035T, was isolated from enrichment sediment samples of a saline lake in Xinjiang Uygur Autonomous Region, PR China. The taxonomic position of the isolate was determined using the polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain EGI FJ00035T formed a distinct clade with 'Chelativorans alearense' UJN715 and 'Chelativorans xinjiangense' lm93 with sequence similarities of 98.44 and 98.22 %, respectively, while sharing less than 96.7 % with other valid type strains. The novel isolate could be distinguished from other species of the genus Chelativorans by its distinct phenotypic, physiological, and genotypic characteristics. Optimal growth of strain EGI FJ00035T occurred on marine agar 2216 at pH 7.0 and 30 °C. The major respiratory quinone was Q-10, while the major fatty acids (>5 %) were C19 : 0 cyclo ω8c, summed feature 8 (C17 : 1 ω6c and/or C17 : 1 ω7c), C16 : 0, C18 : 0, and iso-C17 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipids, unidentified glycolipids, and an unidentified lipid. Based on its genome sequence, the G+C content of strain EGI FJ00035T was 63.2 mol%. The average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values of strain EGI FJ00035T against related members of the genus Chelativorans were below the thresholds for delineation of a novel species. According our polyphasic taxonomic data, strain EGI FJ00035T represents a new species of the genus Chelativorans, for which the name Chelativorans salis sp. nov. is proposed. The type strain of the proposed novel isolate is EGI FJ00035T (=KCTC 92251T=CGMCC 1.19480T).

Spatially resolved current density distribution in GaN-based flip-chip green mini-LEDs by microscopic hyperspectral imaging and modified two-level modeling.

A modified two-level model is proposed to study the spatially resolved current density distribution of GaN-based green miniaturized light-emitting diodes (mini-LEDs), combining with microscopic hyperspectral imaging. We found that the spatially resolved current density distribution reveals both the radiative and non-radiative recombination mappings, which can also be provided separately by this model. In addition, higher current density is not necessarily correlated with higher photon emission, especially for the regions around the electrode edges, where the high current density suggests current crowding and defect-related non-radiative recombination. The current density distribution of mini-LEDs is further verified by the laser-beam-induced current (LBIC) and the spatially resolved mappings of peak wavelength and FWHM. The modified two-level model also offers radiative/non-radiative mappings and is proved to be beneficial to determine the micro-zone current density distribution and to reveal the intrinsic radiative/non-radiative recombination mechanism of mini-LEDs.

Dissecting the networks underlying diverse brain disorders after prenatal glucocorticoid overexposure.

New human life begins in the uterus in a period of both extreme plasticity and sensitivity to environmental disturbances. The fetal stage is also a vital period for central nervous system development, with experiences at this point profoundly and permanently shaping brain structure and function. As such, some brain disorders may originate in utero. Glucocorticoids, a class of essential stress hormones, play indispensable roles in fetal development, but overexposure may have lasting impacts on the brain. In this review, we summarize data from recent clinical and non-clinical studies regarding alterations in fetal brains due to prenatal glucocorticoid overexposure that are associated with nervous system disorders. We discuss relevant changes to brain structure and cellular functions and explore the underlying molecular mechanisms. In addition, we summarize factors that may cause differential outcomes between varying brain regions, and outline clinically feasible intervention strategies that are expected to minimize negative consequences arising from fetal glucocorticoid overexposure. Finally, we highlight the need for experimental evidence aided by new technologies to clearly determine the effects of excessive prenatal glucocorticoid exposure. This review consolidates diverse findings to help researchers better understand the relationship between the prenatal glucocorticoid overexposure and the effects it has on various fetal brain regions, promoting further development of critical intervention strategies.

A bibliometric study on trends in chiropractic research from 1920 to 2023.

OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.

Identifying influential nodes based on the disassortativity and community structure of complex network.

The complex networks exhibit significant heterogeneity in node connections, resulting in a few nodes playing critical roles in various scenarios, including decision-making, disease control, and population immunity. Therefore, accurately identifying these influential nodes that play crucial roles in networks is very important. Many methods have been proposed in different fields to solve this issue. This paper focuses on the different types of disassortativity existing in networks and innovatively introduces the concept of disassortativity of the node, namely, the inconsistency between the degree of a node and the degrees of its neighboring nodes, and proposes a measure of disassortativity of the node (DoN) by a step function. Furthermore, the paper analyzes and indicates that in many real-world network applications, such as online social networks, the influence of nodes within the network is often associated with disassortativity of the node and the community boundary structure of the network. Thus, the influential metric of node based on disassortativity and community structure (mDC) is proposed. Extensive experiments are conducted in synthetic and real networks, and the performance of the DoN and mDC is validated through network robustness experiments and immune experiment of disease infection. Experimental and analytical results demonstrate that compared to other state-of-the-art centrality measures, the proposed methods (DoN and mDC) exhibits superior identification performance and efficiency, particularly in non-disassortative networks and networks with clear community structures. Furthermore, we find that the DoN and mDC exhibit high stability to network noise and inaccuracies of the network data.

Tandem Vinylogous Aldol and Intramolecular [2 + 2] Cycloaddition toward Benzocyclobutenes by UV Light Photocatalysis.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Transient plasma membrane disruption induced calcium waves in mouse and human corneal epithelial cells.

The purpose of this study was to examine transient plasma membrane disruptions (TPMDs) and TPMD-induced Ca++ waves (TPMD Ca++ Wvs) in human and mouse corneal epithelium (HCEC and MCEC). A multi-photon microscope was used to create laser-induced TPMDs in single cultured cells and in intact ex vivo and in vivo MCECs and ex vivo human cornea rim HCECs. Eye rubbing-induced TPMDs were studied by gentle rubbing with a cotton tipped applicator over a closed eyelid in ex vivo and in vivo MCECs. Ca++ sources for TPMD-induced Ca++ waves were explored using Ca++ channel inhibitors and Ca++-free media. TPMDs and TPMD Ca++ Wvs were observed in all cornea epithelial models examined, often times showing oscillating Ca++ levels. The sarcoplasmic reticulum Ca++ ATPase inhibitors thapsigargin and CPA reduced TPMD Ca++ Wvs. TRP V1 antagonists reduced TPMD Ca++ Wvs in MCECs but not HCECs. Ca++-free medium, 18α-GA (gap junction inhibitor), apyrase (hydrolyzes ATP), and AMTB (TRPM8 inhibitor) did not affect TPMD Ca++ Wvs. These results provide a direct demonstration of corneal epithelial cell TPMDs and TPMDs in in vivo cells from a live animal. TPMDs were observed following gentle eye rubbing, a routine corneal epithelial cell mechanical stress, indicating TPMDs and TPMD Ca++ Wvs are common features in corneal epithelial cells that likely play a role in corneal homeostasis and possibly pathophysiological conditions. Intracellular Ca++ stores are the primary Ca++ source for corneal epithelial cell TPMD Ca++ Wvs, with TRPV1 Ca++ channels providing Ca++ in MCECs but not HCECs. Corneal epithelial cell TPMD Ca++ Wv propagation is not influenced by gap junctions or ATP.

Aluminium tolerance and stomata operation: Towards optimising crop performance in acid soil.

Stomatal operation is crucial for optimising plant water and gas exchange and represents a major trait conferring abiotic stress tolerance in plants. About 56% of agricultural land around the globe is classified as acidic, and Al toxicity is a major limiting factor affecting plant performance in such soils. While most of the research work in the field discusses the impact of major abiotic stresses such as drought or salinity on stomatal operation, the impact of toxic metals and, specifically aluminium (Al) on stomatal operation receives much less attention. We aim to fill this knowledge gap by summarizing the current knowledge of the adverse effects of acid soils on plant stomatal development and operation. We summarised the knowledge of stomatal responses to both long-term and transient Al exposure, explored molecular mechanisms underlying plant adaptations to Al toxicity, and elucidated regulatory networks that alleviate Al toxicity. It is shown that Al-induced stomatal closure involves regulations of core stomatal signalling components, such as ROS, NO, and CO2 and key elements of ABA signalling. We also discuss possible targets and pathway to modify stomatal operation in plants grown in acid soils thus reducing the impact of Al toxicity on plant growth and yield.

SCREENES: Enhancing non-uniform sampling reconstruction for symmetrical NMR spectroscopy.

BACKGROUND: Symmetrical NMR spectroscopy, such as Total Correlation Spectroscopy (TOCSY) and other homonuclear spectroscopy, displays symmetry in chemical shift but are generally not symmetrical in terms of intensity, which constitutes a pivotal branch of multidimensional NMR spectroscopy and offers a robust tool for elucidating the structures and dynamics of complex samples, particularly in the context of biological macromolecules. Non-Uniform Sampling (NUS) stands as a critical technique for accelerating multidimensional NMR experiments. However, symmetrical NMR spectroscopy inherently presents dynamic peak intensities, where cross peaks tend to be substantially weaker compared to diagonal peaks. Recovering these weaker cross peaks from NUS data poses a significant challenge, often resulting in compromised data quality. RESULTS: We enhance the reconstruction quality of NUS symmetrical NMR spectroscopy based on the assumption that the asymmetry in intensity is mild. Regarding the sampling schedule, we employ the symmetrical sampling structure integrated with Poisson sampling schedule to enhance the efficiency of data acquisition. In term of the reconstruction algorithm, we propose the new method by incorporating hard and soft symmetrical constraints into our recently developed L1-norm-based Compressed Sensing (CS) method known as Sparse Complex-valued REconstruction Enabled by Newton method (SCREEN). Additionally, we propose a two-step reconstruction strategy that separately addresses diagonal and cross peaks. In this two-step strategy, cross peaks are effectively reconstructed by excluding the stronger diagonal peaks. Extensive experimental results validate the effectiveness of our proposed methodology. SIGNIFICANCE: This method enhances the overall quality of the reconstructed NUS symmetrical NMR spectra, especially in terms of cross peaks, thereby enriching the interpretation of spectral information. Furthermore, it boosts the robustness towards regularization parameters, facilitating a user-friendly experience.

CTCOSY-JRES: A high-resolution three-dimensional NMR method for unveiling J-couplings.

Two-dimensional (2D) J-resolved spectroscopy provides valuable information on J-coupling constants for molecular structure analysis by resolving one-dimensional (1D) spectra. However, it is challenging to decipher the J-coupling connectivity in 2D J-resolved spectra because the J-coupling connectivity cannot be directly provided. In addition, 2D homonuclear correlation spectroscopy (COSY) can directly elucidate molecular structures by tracking the J-coupling connectivity between protons. However, this method is limited by the problem of spectral peak crowding and is only suitable for simple sample systems. To fully understand the intuitive coupling relationship and coupling constant information, we propose a three-dimensional (3D) COSY method called CTCOSY-JRES (Constant-Time COrrelation SpectroscopY and J-REsolved Spectroscopy) in this paper. By combining the J-resolved spectrum with the constant-time COSY technique, a doubly decoupled COSY spectrum can be provided while preserving the J-coupling constant along an additional dimension, ensuring high-resolution analysis of J-coupling connectivity and J-coupling information. Moreover, compression sensing and fold-over correction techniques are introduced to accelerate experimental acquisition. The CTCOSY-JRES method has been successfully validated in a variety of sample systems, including industrial, agricultural, and biopharmaceutical samples, revealing complex coupling interactions and providing deeper insights into the resolution of molecular structures.

A combination of QTL mapping and genome-wide association study revealed the key gene for husk number in maize.

KEY MESSAGE: Two key genes Zm00001d021232 and Zm00001d048138 were identified by QTL mapping and GWAS. Additionally, they were verified to be significantly associated with maize husk number (HN) using gene-based association study. As a by-product of maize production, maize husk is an important industrial raw material. Husk layer number (HN) is an important trait that affects the yield of maize husk. However, the genetic mechanism underlying HN remains unclear. Herein, a total of 13 quantitative trait loci (QTL) controlling HN were identified in an IBM Syn 10 DH population across different locations. Among these, three QTL were individually repeatedly detected in at least two environments. Meanwhile, 26 unique single nucleotide polymorphisms (SNPs) were detected to be significantly (p < 2.15 × 10-6) associated with HN in an association pool. Of these SNPs, three were simultaneously detected across multiple environments or environments and best linear unbiased prediction (BLUP). We focused on these environment-stable and population-common genetic loci for excavating the candidate genes responsible for maize HN. Finally, 173 initial candidate genes were identified, of which 22 were involved in both multicellular organism development and single-multicellular organism process and thus confirmed as the candidate genes for HN. Gene-based association analyses revealed that the variants in four genes were significantly (p < 0.01/N) correlated with HN, of which Zm00001d021232 and Zm00001d048138 were highly expressed in husks and early developing ears among different maize tissues. Our study contributes to the understanding of genetic and molecular mechanisms of maize husk yield and industrial development in the future.

Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs.

G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors H2R and H3R couple with Gs- or Gi-proteins respectively. Here, three cryo-EM structures of H2R-Gs and H3R-Gi complexes are presented at a global resolution of 2.6-2.7 Å. These structures reveal the unique binding pose for endogenous histamine in H3R, wherein the amino group interacts with E2065.46 of H3R instead of the conserved D1143.32 of other aminergic receptors. Furthermore, comparative analysis of the H2R-Gs and H3R-Gi complexes reveals that the structural geometry of TM5/TM6 determines the primary G-protein selectivity in histamine receptors. Machine learning (ML)-based structuromic profiling and functional analysis of class A GPCR-G-protein complexes illustrate that TM5 length, TM5 tilt, and TM6 outward movement are key determinants of the Gs and Gi/o selectivity among the whole Class A family. Collectively, the findings uncover the common structural geometry within class A GPCRs that determines the primary Gs- and Gi/o-coupling selectivity.

Novel Superhydrophobic Copper Mesh-Based Centrifugal Device for Edible Oil-Water Separation.

Edible oil is essential for people's daily life but also results in a large amount of oily wastewater simultaneously. Oil-water separation is a practical route that can not only purify wastewater but also recycle valuable edible oil. In this study, the superhydrophobic copper mesh (SCM) was prepared by chemical etching, and a novel oil-water centrifugal device was designed for high-efficiency separation of edible oil wastewater. The kernel is a self-prepared SCM, which has a water contact angle (WCA) of 155.1 ± 1.8° and an oil contact angle (OCA) of 0°. Besides, the separation performance of the SCM for edible oil-water mixtures was studied in this study. The results showed that the SCM exhibited excellent oil/water separation performance, with a separation efficiency of up to 96.7% for sunflower seed oil-water wastewater, 93.3% for corn oil-water wastewater, and 98.3% for peanut oil-water wastewater, respectively. Moreover, the separation efficiency was still over 90% after 18 cycles. A model was established to analyze the oil-water separation mechanism via centrifugation. The oil-water centrifugal separation device has great potential for scale-up applications.

Evolution of reactive oxygen species cellular targets for plant development.

Reactive oxygen species (ROS) are the key players in regulating developmental processes of plants. Plants have evolved a large array of gene families to facilitate the ROS-regulated developmental process in roots and leaves. However, the cellular targets of ROS during plant evolutionary development are still elusive. Here, we found early evolution and large expansions of protein families such as mitogen-activated protein kinases (MAPK) in the evolutionarily important plant lineages. We review the recent advances in interactions among ROS, phytohormones, gasotransmitters, and protein kinases. We propose that these signaling molecules act in concert to maintain cellular ROS homeostasis in developmental processes of root and leaf to ensure the fine-tuning of plant growth for better adaptation to the changing climate.

A case of multiple ART intolerance responds to Albuvirtide and Dolutegravir: Case report and literature review.

Upon confirming an HIV diagnosis, patients need to start life-long antiretroviral therapy (ART) as soon as possible. During HIV treatment, ART drugs can cause intolerable adverse reactions, leading to poor medication compliance, treatment failure, and advancement of the HIV stage. Herein, we report a case of AIDS intolerant to multiple antiviral drugs due to side effects that we finally stabilized with the Albuvirtide (ABT) and Dolutegravir (DTG) combination. A 48 -year-old woman developed intractable nausea, vomiting and abdominal discomfort within one month of starting ART. Over the course of four years, she was switched to four different ART regimens due to her intolerance of severe adverse effects, mainly gastrointestinal symptoms, rash, and lethargy. Over four years, she failed to attain viral suppression due to poor drug compliance. After several ART changes, we started her on the Long-acting antiretroviral therapy (LA ART), Albuvirtide, combined with Dolutegravir, which she tolerated well. The patient's general condition improved significantly and attained marked virologic suppression. The patient's condition has been well controlled for nearly two years with good adherence. This case emphasizes the influence of ART treatment options on medication compliance and the outcome of HIV infection.