Hierarchically engineered nanostructures from compositionally anisotropic molecular building blocks.

The inability to synthesize hierarchical structures with independently tailored nanoscale and mesoscale features limits the discovery of next-generation multifunctional materials. Here we present a predictable molecular self-assembly strategy to craft nanostructured materials with a variety of phase-in-phase hierarchical morphologies. The compositionally anisotropic building blocks employed in the assembly process are formed by multicomponent graft block copolymers containing sequence-defined side chains. The judicious design of various structural parameters in the graft block copolymers enables broadly tunable compositions, morphologies and lattice parameters across the nanoscale and mesoscale in the assembled structures. Our strategy introduces advanced design principles for the efficient creation of complex hierarchical structures and provides a facile synthetic platform to access nanomaterials with multiple precisely integrated functionalities.

Correction: Cross-linkable, phosphobetaine-based, zwitterionic amphiphiles that form lyotropic bicontinuous cubic phases.

Correction for 'Cross-linkable, phosphobetaine-based, zwitterionic amphiphiles that form lyotropic bicontinuous cubic phases' by Lauren N. Bodkin et al., Soft Matter, 2023, 19, 3768-3772, https://doi.org/10.1039/D3SM00269A.

Cross-linkable, phosphobetaine-based, zwitterionic amphiphiles that form lyotropic bicontinuous cubic phases.

The design, synthesis, and lyotropic liquid crystal phase behaviour of six cross-linkable, phosphobetaine-based, zwitterionic amphiphiles are described. Two form a QII phase with aq. NH4Cl solution, giving 3D-nanoporous membrane materials that can be used for water desalination and are not susceptible to ion exchange like traditional ionic analogues.

Clinical characteristics, treatment, and outcome of low-risk non-HIV-associated cryptococcal meningitis: A retrospective cohort study.

Although non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is a severe disease, there are still some non-HIV CM patients with a low risk of therapeutic failure. Recognizing clinical characteristics of low-risk non-HIV-associated CM may enable clinicians to treat non-HIV-associated CM more reasonably. According to the definition of low-risk non-HIV-associated CM in the 2010 Infectious Diseases Society of America guideline, a total of 220 non-HIV CM patients were divided into two groups (Group 1: 35 low-risk patients and Group 2: 185 non-low-risk patients). Clinical characteristics, treatment, and outcome were compared between the two groups. Compared with non-low-risk patients, low-risk patients had a lower rate of headache (82.9% vs. 95.7%, P = .012), cerebrospinal fluid (CSF) opening pressure (OP) at baseline (CSF OP < 250-mm H2O, 60.0% vs. 32.4%, P = .001), and baseline CSF cryptococcal count (median, 0 vs. 2376, P < .001), higher baseline CSF white blood cell (median, 130 vs. 90, P = .029) and CSF protein (median, 0.87 vs. 0.73, P = .011). Multivariate analysis showed that baseline CSF OP <250-mm H2O (OR: 2.545, 95% CI 1.168, 5.545, P = .019) was independently associated with low-risk for non-HIV-associated CM. The lengths of AMB-d-based induction therapy of low-risk patients (median, 20 days) were shorter (P < .001) than that of non-low-risk patients (median, 38 days). The successful outcome rate of low-risk patients was higher than non-low-risk patients (97.1% vs. 54.6%, P < .001). We demonstrated that non-HIV-associated CM patients with baseline CSF OP < 250-mm H2O were prone to the low-risk status.

This was a retrospective cohort study to find the features of low-risk non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM). We found that non-HIV-associated CM patients with baseline cerebrospinal fluid opening pressure <250-mm H2O were prone to low-risk status.

[Effect of arterial flow on muscle atrophy].

This study analyzed the inherent relation between arterial blood mass flow and muscle atrophy of residual limb to provide some necessary information and theoretical support for the clinical rehabilitation of lower limb amputees. Three-dimensional arterial model reconstruction was performed on both intact side and residual limb of a unilateral transfemoral amputee who is the subject. Then hemodynamic calculation was carried out to comparatively analyze the mass flow state at each arterial outlet of both lower extremities. The muscle atrophy ratio of residual limb was calculated by measuring the cross-sectional area of bilateral muscles. Based on the blood supply relationship, the correlation between arterial blood flow reduction ratio and muscle atrophy ratio was discussed. The results showed that the mass flow of superficial femoral arteries and lateral circumflex femoral arteries severely reduced. Meanwhile rectus femoris, vastus lateralis and vastus medialis which were fed by these arteries showed great atrophy too. On the contrary, the mass flow of deep femoral arteries and medial femoral circumflex arteries slightly reduced. Meanwhile gracilis, adductor longus, long head of biceps which were fed by these arteries showed mild atrophy too. These results indicated that there might be a positive and promotion correlation between the muscle atrophy ratio and the blood mass flow reduction ratio of residual limb during rehabilitation.

Development of an injectable oxidized dextran/gelatin hydrogel capable of promoting the healing of alkali burn-associated corneal wounds.

The cornea serves as an essential shield that protects the underlying eye from external conditions, yet it remains highly vulnerable to injuries that could lead to blindness and scarring if not promptly and effectively treated. Excessive inflammatory response constitute the primary cause of pathological corneal injury. This study aimed to develop effective approaches for enabling the functional repair of corneal injuries by combining nanoparticles loaded with anti-inflammatory agents and an injectable oxidized dextran/gelatin/borax hydrogel. The injectability and self-healing properties of developed hydrogels based on borate ester bonds and dynamic Schiff base bonds were excellent, improving the retention of administered drugs on the ocular surface. In vitro cellular assays and in vivo animal studies collectively substantiated the proficiency of probucol nanoparticle-loaded hydrogels to readily suppress proinflammatory marker expression and to induce the upregulation of anti-inflammatory mediators, thereby supporting rapid repair of rat corneal tissue following alkali burn-induced injury. As such, probucol nanoparticle-loaded hydrogels represent a prospective avenue to developing long-acting and efficacious therapies for ophthalmic diseases.

Characteristics of Design and Analysis of Ophthalmic Randomized Controlled Trials: A Review of Ophthalmic Papers 2020-2021.

Objective: To evaluate the recent practice of design and statistical analysis of ophthalmic randomized clinical trials (RCTs). Design: Review of 96 ophthalmic RCTs. Methods: Two authors (R.D., G.S.Y.) reviewed primary result papers published from January 2020 through December 2021 in Ophthalmology, JAMA Ophthalmology, American Journal of Ophthalmology, and British Journal of Ophthalmology. Data were extracted and analyzed for the characteristics of design (1-eye design, 2-eye design, paired-eye design, and subject design), sample size and power, and statistical analysis for intereye correlation adjustment, missing data, and correction for multiplicity. Main Outcome Measures: Characteristics of trial design and statistical analysis. Results: Among 96 RCTs, 50 (52%) used 1-eye design, 21 (22%) 2-eye design, 10 (10%) paired-eye design, and 15 (16%) subject design. In 31 trials of 2-eye design or paired-eye design, 18 (58%) trials had suboptimal analysis of data from both eyes by analyzing data from 1 eye (n = 10), taking the average of 2 eyes (n = 2), analyzing 2 eyes separately (n = 1), ignoring intereye correlation (n = 3), or not specifying how 2-eye data were analyzed (n = 2), and 13 trials (42%) properly adjusted the intereye correlation by using the mixed-effects model (n = 6), paired t test (n = 5), generalized estimating equations (n = 1), or marginal Cox regression model (n = 1). Among 96 trials, 75 (78%) provided both sample size and statistical power estimation, and 16 (17%) trials described statistical test for sample size or power estimation. Missing data in primary outcome occurred in 86 (90%) trials with a median missing data rate of 8%, 32 (37%) trials applied statistical methods for missing data, including last value carried forward (n = 10), multiple imputation (n = 14), or other approaches (n = 8). Among 25 trials with > 2 arms, 16 (64%) corrected for multiplicity using the Bonferroni procedure (n = 8), Hochberg procedure (n = 2), Gatekeeping procedure (n = 2), or hierarchical procedure (n = 4). Among 16 trials with multiple primary outcomes, 4 (25%) corrected for multiplicity by the Bonferroni procedure. Conclusions: There are opportunities for improvement in the design and statistical analyses of ophthalmic trials, particularly in the aspects of adjustment for intereye correlation, missing data, and multiplicity. Continuing education in ophthalmology and vision research community may improve the quality of ophthalmic trials. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Remodeling of the cardiovascular hemodynamic environment by lower limb heat exposure: A computational fluid dynamic study.

BACKGROUND: Lower limb heat exposure (LLHE) is a promising strategy for the daily management of cardiovascular health because of its non-pharmaceutical advantages. To support the application of this strategy in cardiovascular protection, we examined its impact on the global hemodynamic environment. METHODS: Skin blood flow (SBF) of eight locations on the lower limbs was measured before and after LLHE (40 °C and 44 °C) in ten healthy subjects by using a laser Doppler flowmeter. A closed-loop model of circulation uses changes in SBF to quantify the influence of LLHE on the blood flow of the arterial trunk (from ascending aorta to the femoral artery) and visceral branches (coronary, celiac, renal, and mesenteric arteries). RESULTS: The SBF in all locations tested on the lower limbs increased significantly (p<0.001) with LLHE and a 3.39-fold and 7.40-fold increase in mean SBF were observed under 40 °C and 44 °C conditions, respectively. In the model, the peak (3.9-25.1%), end-diastolic (13.7-107.3%), and mean blood flow (8.5-86.5%) in the arterial trunk increased with the increase in temperature, but the retrograde flow in the thoracic aorta and abdominal aorta Ⅰ increased at least twice in the diastolic period. Furthermore, LLHE also increased the blood flow of the visceral branches (2.5-20.7%). CONCLUSION: These findings suggest that LLHE is expected to be a daily strategy for enhancing the functions of both the arterial trunk and visceral arteries, but the increased blood flow reversal in the thoracic and abdominal aortas warrants further investigation.

Tunable organic solvent nanofiltration in self-assembled membranes at the sub-1 nm scale.

Organic solvent-stable membranes exhibiting strong selectivity and high permeance have the potential to transform energy utilization in chemical separation processes. A key goal is developing materials with uniform, well-defined pores at the 1-nm scale, with sizes that can be tuned in small increments with high fidelity. Here, we demonstrate a class of organic solvent-stable nanoporous membranes derived from self-assembled liquid crystal mesophases that display such characteristics and elucidate their transport properties. The transport-regulating dimensions are defined by the mesophase geometry and can be controlled in increments of ~0.1 nm by modifying the chemical structure of the mesogen or the composition of the mesophase. The highly ordered nanostructure affords previously unidentified opportunities for the systematic design of organic solvent nanofiltration membranes with tailored selectivity and permeability and for understanding and modeling rejection in nanoscale flows. Hence, these membranes represent progress toward the goal of enabling precise organic solvent nanofiltration.

Reallocation of cutaneous and global blood circulation during sauna bathing through a closed-loop model.

OBJECTIVE: Sauna bathing (SB) is an important strategy in cardiovascular protection, but there is no mathematical explanation for the reallocation of blood circulation during heat-induced superficial vasodilation. We sought to reveal such reallocation via a simulated hemodynamic model. METHODS: A closed-loop cardiovascular model with a series of electrical parameters was constructed. The body surface was divided into seven blocks and each block was modeled by a lumped resistance. These resistances were adjusted to increase skin blood flow (SBF), with the aim of reflecting heat-induced vasodilation during SB. Finally, the blood pressure was compared before and after SB, and the blood flow inside the aorta and visceral arteries were also analyzed. RESULTS: With increasing SBF in this model, the systolic, diastolic, and mean blood pressure in the arterial trunk decreased by 13-29, 18-36, and 19-37 mmHg, respectively. Despite the increase in the peak and mean blood flow in the arterial trunk, the diastolic blood flow reversal in the thoracic and abdominal aortas increased significantly. Nevertheless, the blood supply to the heart, liver, stomach, spleen, kidney, and intestine decreased by at least 25%. Moreover, the pulmonary blood flow increased significantly. CONCLUSION: Simulated heat-induced cutaneous vasodilation in this model lowers blood pressure, induces visceral ischemia, and promotes pulmonary circulation, suggesting that the present closed-loop model may be able to describe the effect of sauna bathing on blood circulation. However, the increase of retrograde flow in the aortas found in this model deserves further examination.

Two-Photon Laser Microprinting of Highly Ordered Nanoporous Materials Based on Hexagonal Columnar Liquid Crystals.

Nanoporous materials relying on supramolecular liquid crystals (LCs) are excellent candidates for size- and charge-selective membranes. However, whether they can be manufactured using printing technologies remained unexplored so far. In this work, we develop a new approach for the fabrication of ordered nanoporous microstructures based on supramolecular LCs using two-photon laser printing. In particular, we employ photo-cross-linkable hydrogen-bonded complexes, that self-assemble into columnar hexagonal (Colh) mesophases, as the base of our printable photoresist. The presence of photopolymerizable groups in the periphery of the molecules enables the printability using a laser. We demonstrate the conservation of the Colh arrangement and of the adsorptive properties of the materials after laser microprinting, which highlights the potential of the approach for the fabrication of functional nanoporous structures with a defined geometry. This first example of printable Colh LC should open new opportunities for the fabrication of functional porous microdevices with potential application in catalysis, filtration, separation, or molecular recognition.

Protective Effect of Organic Selenium on Oxidative Damage and Inflammatory Reaction of Rabbit Kidney Induced by T-2 Toxin.

T-2 toxin is a member of a class of mycotoxins produced by a variety of Fusarium species under appropriate temperature and humidity conditions and is a common contaminant in food and feedstuffs of cereal origin. Selenium is an indispensable element in animals, regulates a variety of biological functions of the body, and can antagonize metal and mycotoxin poisoning to a certain extent. However, the effect of selenium on kidney injury induced by T-2 toxin has not been reported. In this study, 50 New Zealand rabbits were divided into 5 groups (the control group, T-2 toxin group, low-dose Se + T-2 toxin group, medium-dose Se + T-2 toxin group, and high-dose Se + T-2 toxin group). Rabbits were examined after oral administration of different doses of selenomethionine (SeMet) for 21 days and after perfusion with 0.4 mg/kg T-2 toxin (or the same dose of olive oil in the control group) for 5 days. We found that T-2 toxin induced kidney function damage and increased the levels of ROS and the contents of inflammatory factors. Renal structure was pathologically damaged. However, we found that after pretreatment with 0.2 mg/kg SeMet, oxidative stress, the inflammatory response, and pathological damage induced by T-2 toxin were attenuated. The results indicate that a low dose (0.2 mg/kg) of SeMet effectively reversed T-2 toxin-induced kidney injury in rabbits.

Elucidating the Mechanism of Fast Na Storage Kinetics in Ether Electrolytes for Hard Carbon Anodes.

The sodium storage performance of a hard carbon (HC) anode in ether electrolytes exhibits a higher initial Coulombic efficiency (ICE) and better rate performance compared to conventional ester electrolytes. However, the mechanism behind faster Na storage kinetics for HC in ether electrolytes remains unclear. Herein, a unique solvated Na+ and Na+ co-intercalation mechanism in ether electrolytes is reported using designed monodispersed HC nanospheres. In addition, a thin solid electrolyte interphase film with a high inorganic proportion formed in an ether electrolyte is visualized by cryo transmission electron microscopy and depth-profiling X-ray photoelectron spectroscopy, which facilitates Na+ transportation, and results in a high ICE. Furthermore, the fast solvated Na+ diffusion kinetics in ether electrolytes are also revealed via molecular dynamics simulation. Owing to the contribution of the ether electrolytes, an excellent rate performance (214 mAh g-1 at 10 A g-1 with an ultrahigh plateau capacity of 120 mAh g-1 ) and a high ICE (84.93% at 1 A g-1 ) are observed in a half cell; in a full cell, an attractive specific capacity of 110.3 mAh g-1 is achieved after 1000 cycles at 1 A g-1 .

Rapid Fabrication by Lyotropic Self-Assembly of Thin Nanofiltration Membranes with Uniform 1 Nanometer Pores.

Nanostructured materials with precisely defined and water-bicontinuous 1-nm-scale pores are highly sought after as advanced materials for next-generation nanofiltration membranes. While several self-assembled systems appear to satisfy this need, straightforward fabrication of such materials as submicron films with high-fidelity retention of their ordered nanostructure represents a nontrivial challenge. We report the development of a lyotropic liquid crystal mesophase that addresses the aforementioned issue. Films as thin as ∼200 nm are prepared on conventional support membranes using solution-based methods. Within these films, the system is composed of a hexagonally ordered array of ∼3 nm diameter cylinders of cross-linked polymer, embedded in an aqueous medium. The cylinders are uniformly oriented in the plane of the film, providing a transport-limiting dimension of ∼1 nm, associated with the space between the outer surfaces of nearest-neighbor cylinders. These membranes exhibit molecular weight cutoffs of ∼300 Da for organic solutes and are effective in rejecting dissolved salts, and in particular, divalent species, while exhibiting water permeabilities that rival or exceed current state-of-the-art commercial nanofiltration membranes. These materials have the ability to address a broad range of nanofiltration applications, while structure-property considerations suggest several avenues for potential performance improvements.

Protective effect of selenomethionine on intestinal injury induced by T- 2 toxin.

T-2 toxin is the most toxic as a type A trichothecenes, which could contaminate grains, especially in wheat and corn. It can cause immune suppression, neurotoxicity, the apoptosis of cells and even induce tumorigenesis. Recent studies have indicated that selenium (Se) have protective effect against mycotoxins-induced toxicity. The present studies was designed to investigate the protective role of Selenomethionine (SeMet) on T-2 toxin-induced toxicity in rabbit's jejunum. 50 New Zealand rabbits were divided into five group (Control group, T-2 group, low-dose Se + T-2 group, medium-dose + T-2 group and high-dose Se + T-2 group). New Zealand rabbits were orally administered with SeMet (0.2, 0.4 and 0.6 mg/kg, Adding diet) for 21 days. On 17th days, each group began to take 0.4 mg/kg of T-2 toxin orally every day for 5 days. We found that rabbit exposed to T-2 toxin could increase the levels of ROS, and decrease activities of antioxidant enzymes and the expression of Occludin and ZO-1. In addition, T-2 toxin could trigger jejunal inflammatory response and enhance the expression of IL-1ß, IL-6 and TNF-α. After SeMet pretreatment, our results indicated that Se attenuated the T-2 toxin-induced oxidative stress, decreasing the level of ROS, MDA and enhancing the activity of SOD and GSH-Px. Moreover, SeMet can alleviate jejunal inflammatory response, and protect the integrity of the intestinal barrier through up-regulating the expression of ZO-1 and Occludin. In the present research, supplementation of 0.2 mg/kg SeMet in the diet could effectively alleviate the T-2 toxin poisoning in rabbits.

Hyperaccumulation Route to Ca-Rich Hard Carbon Materials with Cation Self-Incorporation and Interlayer Spacing Optimization for High-Performance Sodium-Ion Batteries.

The hard carbon (HC) has been emerging as one of the most promising anode materials for sodium-ion batteries (SIBs). Incorporation of cations into the HC lattice proved to be effective to regulate their d-interlayer spacing with a modified SIB performance. However, the complexity and high cost of current synthetic processes limited its large-scale application in SIBs. Through the natural hyperaccumulation process, a cost-effective and scale-up-driven procedure to produce Ca-ion self-incorporated HC materials was proposed by applying tamarind fruits as the precursor with the enrichment of Ca ions. In virtue of one-step pyrolysis, the self-incorporated and well-distributed Ca ions in tamarind fruits had successfully served as the buffer layer to expand the d-interlayer spacing of HC materials. Furthermore, the natural porosity hierarchy could be largely preserved by the optimization of calcination temperature. As a result, the Ca-rich HC material had exhibited the optimized cycling performance (326.7 mA h g-1 at 50 mA g-1 and capacity retention rate of 89.40% after 250 cycles) with a high initial Coulombic efficiency of 70.39%. This work provided insight into applying the hyperaccumulation effect of biomass precursors to produce doped HC materials with ion self-incorporation and the optimized d-interlayer spacing, navigating its large-scale application for high-performance SIBs.

Therapeutic effects of nerve leachate-treated adipose-derived mesenchymal stem cells on rat sciatic nerve injury.

Peripheral nerve injury (PNI) is a common condition, often resulting from physical nerve injury and trauma. Successful repair of the peripheral nerve is dependent on the regenerative activity of Schwann cells (SCs). Application of SC-like adipose-derived mesenchymal stem cells (ADSCs) may be a suitable cell-based therapy for PNI. In the present study, nerve leachate derived from the rat sciatic nerve was used to induce the differentiation of ADSCs. These cells were placed in an acellular biological scaffold, which was then grafted to a rat sciatic nerve to bridge a 1-cm gap. Sprague-Dawley rats were divided into four groups: Scaffold only, untreated ADSCs + scaffold, nerve leachate-treated ADSCs + scaffold and autograft. Two-months post-transplant, the structure and function of the regenerated nerves and the recovery of the innervated muscles was analyzed. After transplant, there was a significant increase in the average area (15.86%; P<0.05), density (23.13%; P<0.05) and thickness (43.24%; P<0.05) of regenerated nerve fibers in the nerve leachate-treated ADSCs + scaffold group compared with the untreated ADSCs + scaffold group. The nerve conduction velocity in the nerve leachate-treated ADSCs + scaffold and autograft groups was superior to that in the other groups. In the nerve leachate-treated ADSCs + scaffold group, the cross-sectional area of the gastrocnemius increased by 39.28% (P<0.05) and the cross-sectional area of collagen fibers decreased by 29.87% (P<0.05) compared with the ADSCs + scaffold group. Moreover, the therapeutic effect of nerve leachate-treated ADSCs + scaffold on PNI was similar to that of an autograft. These results suggest that nerve leachate-treated ADSCs may promote the repair of PNI.

MSC-Derived Exosomes-Based Therapy for Peripheral Nerve Injury: A Novel Therapeutic Strategy.

Although significant advances have been made in synthetic nerve conduits and surgical techniques, complete regeneration following peripheral nerve injury (PNI) remains far from optimized. The repair of PNI is a highly heterogeneous process involving changes in Schwann cell phenotypes, the activation of macrophages, and the reconstruction of the vascular network. At present, the efficacy of MSC-based therapeutic strategies for PNI can be attributed to paracrine secretion. Exosomes, as a product of paracrine secretion, are considered to be an important regulatory mediator. Furthermore, accumulating evidence has demonstrated that exosomes from mesenchymal stem cells (MSCs) can shuttle bioactive components (proteins, lipids, mRNA, miRNA, lncRNA, circRNA, and DNA) that participate in almost all of the abovementioned processes. Thus, MSC exosomes may represent a novel therapeutic tool for PNI. In this review, we discuss the current understanding of MSC exosomes related to peripheral nerve repair and provide insights for developing a cell-free MSC therapeutic strategy for PNI.

Lotus Seedpod-Derived Hard Carbon with Hierarchical Porous Structure as Stable Anode for Sodium-Ion Batteries.

Hard carbon material is one of the candidates with great promise as anode-active material for sodium-ion batteries (SIBs). Here, new types of biomass-derived hard carbons were obtained via one-step carbonization of lotus seedpods at 1000-1400 °C, respectively. The control of carbonization temperature proved to be significant in controlling the lattice characterization of lotus seedpod-derived hard carbon. Higher temperature generally promoted the lattice graphitization and thus generated a more narrowed d-interlayer space with limited pore volume. The hard carbon pyrolyzed at 1200 °C achieved an optimized reversible capacity of 328.8 mAh g-1 and exhibited a remarkable capacity retention of 90% after 200 cycles. In addition, such a biomass-derived hard carbon presented improved cyclic stability and rate performance, revealing capacity of 330.6, 288.9, 216.9, 116.5, and 78.3 mAh g-1 at 50, 100, 200, 500, and 1000 mA g-1, respectively. Intrinsically, high pyrolysis temperature (1400 °C) gave rise to more narrowed carbon lattice and reduced pore volume and, thus, failed to accommodate sodium ions either from the intercalation into lattice or the ion adsorption onto the pore surface. Such combined advantages of lotus seedpod-derived hard carbon, including the abundance, sufficiently adequate reversible capacity, and prominent cycling and rate property allowed for its large-scale application as promising anode material for SIBs.

The Upstream Pathway of mTOR-Mediated Autophagy in Liver Diseases.

Autophagy, originally found in liver experiments, is a cellular process that degrades damaged organelle or protein aggregation. This process frees cells from various stress states is a cell survival mechanism under stress stimulation. It is now known that dysregulation of autophagy can cause many liver diseases. Therefore, how to properly regulate autophagy is the key to the treatment of liver injury. mechanistic target of rapamycin (mTOR)is the core hub regulating autophagy, which is subject to different upstream signaling pathways to regulate autophagy. This review summarizes three upstream pathways of mTOR: the phosphoinositide 3-kinase (PI3K)/protein kinase (AKT) signaling pathway, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, and the rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-extracellular activated protein kinase kinase (MEK)/ extracellular-signal-regulated kinase (ERK) signaling pathway, specifically explored their role in liver fibrosis, hepatitis B, non-alcoholic fatty liver, liver cancer, hepatic ischemia reperfusion and other liver diseases through the regulation of mTOR-mediated autophagy. Moreover, we also analyzed the crosstalk between these three pathways, aiming to find new targets for the treatment of human liver disease based on autophagy.