Compiling and applying atmospheric resource balance sheet in off-office auditing of leading cadres in China.

Atmospheric resources provide important support for human economic and social systems through their unique ecosystem service functions. Implementing the off-office auditing of atmospheric resources for leading cadres holds great strategic significance for fundamentally solve air pollution problems. Exploring the compilation of an atmospheric resource balance sheet is a necessary pre-step in the implementation of outgoing audits. In this paper, atmospheric resources are innovatively divided into atmospheric capacity resources and atmospheric quality resources from the perspective of the ecosystem service functions of atmospheric resources. The value of atmospheric resource assets is calculated by combining the environmental capacity value method and the environmental loss evaluation method. This study evaluates atmospheric ecological achievements based on the atmospheric resources balance sheet and related accounts as the data carrier and opens up the key "blocking point" of the off-office auditing of atmospheric resources. This paper takes Anhui Province as an example and applies the accounting results of the prepared atmospheric resource balance sheet to evaluate the atmospheric resource ecological achievements of leading cadres from 2016 to 2020. The results clearly reflect the ecological achievements and shortcomings of local leading cadres during their tenure.

Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat.

Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.

Molecular eidemiology of carbapenem-resistant Enterobacter cloacae complex in a tertiary hospital in Shandong, China.

BACKGROUND: The increasing incidence and prevalence of carbapenem-resistant Enterobacter cloacae complex (CREC) poses great challenges to infection prevention and disease treatment. However, much remains unknown about the clinical characteristics of CREC isolates. Our objective was to characterize antimicrobial resistance and, carbapenemase production in CREC with 36 CREC isolates collected from a tertiary hospital in Shandong, China. RESULTS: Three types of carbapenemases (NDM, IMP and VIM) were detected in these isolates. Among them, NDM carbapenemases were most prevalent, with a 61.2% (22/36) detection rate for NDM-1, 27.8% (10/36) for NDM-5 and 2.8% (1/36) for NDM-7. IMP-4 was found in two isolates and VIM-1 in only one isolate. The MLST analysis identified 12 different sequence types (STs), of which ST171 (27.8%) was the most prevalent, followed by ST418 (25.0%). ST171 isolates had significantly higher rates of resistance than other STs to gentamicin and tobramycin (Ps < 0.05), and lower rates of resistance to aztreonam than ST418 and other STs (Ps < 0.05). Among 17 carbapenemase-encoding genes, the blaNDM-5 gene was more frequently detected in ST171 than in ST418 and other isolates (Ps < 0.05). In contrast, the blaNDM-1 gene was more frequently seen in ST418 than in ST171 isolates. One novel ST (ST1965) was identified, which carried the blaNDM-1 gene. CONCLUSION: NDM-5 produced by ST171 and NDM-1 carbapenemase produced by ST418 were the leading cause of CREC in this hospital. This study enhances the understanding of CREC strains and helps improve infection control and treatment in hospitals.

[Effects of 24 Years Different Straw Return on Soil Carbon, Nitrogen, Phosphorus, and Extracellular Enzymatic Stoichiometry in Dryland of the Loess Plateau, China].

Exploring the biogeochemical cycle characteristics of soil carbon, nitrogen, and phosphorus in farmland in the dryland of the loess plateau can provide scientific basis and technical support for efficient crop production and sustainable land use. Here, based on a long-term (24 year) straw return field experiment in Shouyang, Shanxi province, the effects of different straw return regimes, i.e., straw mulching (SM), direct straw return (DS), animal-digested straw return (AS), and non-straw return (CK), on the stoichiometric ratio of soil elements and extracellular enzyme activities were studied. The vector angle and length were calculated to indicate the resource constraints faced by microorganisms. The vector angle was greater than 45° and less than 45°, indicating that microorganisms were limited by phosphorus and nitrogen, respectively. The greater the deviation from 45°, the greater the degree of limitation, and the longer the vector length, the more severely limited by carbon. The results showed that ① the soil C/N and C/P of long-term straw returning ranged from 9.81 to 14.28 and from 14.58 to 21.92, with the mean values of 12.36 and 17.51, respectively, which were 6.0% and 4.2% lower than that at the initial stage of the experiment. The soil N/P was distributed between 1.27 and 1.57, with an average of 1.42, which was 2.2% higher than that in the initial stage. The soil C/N and C/P ratios showed a trend of first decreasing and then increasing, the soil N/P ratio basically showed a flat trend, and there was no significant difference in soil element metering ratios between different straw returning treatments. ② Compared with the 24-year long-term non-straw return treatment, the activities of ß-1,4-glucosidase (BG) and ß-1,4-N-acetylglucosaminidase (NAG) in the soil of the long-term straw mulching treatment increased by 134.4% and 107.5% (P<0.05), the activities of BG and alkaline phosphatase (AP) in the soil of the long-term straw mulching treatment decreased by 59.3% and 59.5% (P<0.05), respectively, and the activities of NAG in the soil of the long-term straw mulching treatment increased by 102.8% (P<0.05). Under the long-term straw returning treatment, soil microorganisms were faced with carbon and phosphorus limitation as a whole. Long-term straw mulching aggravated microbial carbon limitation, and animal-digested straw return could alleviate the degree of carbon limitation. Compared with that in the 24-year long-term non-straw return treatment, soil EEAC/N could be significantly reduced by the animal-digested straw return treatment, and soil EEAC/P could be increased by the direct straw return treatment. The three straw returning methods had no significant indigenous effect on soil EEAN/P. The overall vector angle was greater than 45°, and the vector length increased by 3.8%-20.1% compared with that in the initial stage. ③ Correlation analysis showed that C and N inputs were significantly negatively correlated with BG activity; available nitrogen was significantly correlated with NAG activity, AP activity, and EEAC/N; C/P was significantly positively correlated with EEAC/N; there were significant correlations between N/P and NAG activity, AP activity, EEAC/N, and EEAC/P; and there was no significant correlation between EEAN/P and any environmental factors. In conclusion, the availability of soil nitrogen and phosphorus elements and N/P ratio had significant effects on soil extracellular enzyme activity and stoichiometric characteristics under different long-term straw returning treatments. In the future, more attention should be paid to the improvement of organic carbon and the promotion of nitrogen and phosphorus availability in farmland soil in soil-efficient cultivation and agricultural production activities.

Static and Dynamic: Evolving Biomaterial Mechanical Properties to Control Cellular Mechanotransduction.

The extracellular matrix (ECM) is a highly dynamic system that constantly offers physical, biological, and chemical signals to embraced cells. Increasing evidence suggests that mechanical signals derived from the dynamic cellular microenvironment are essential controllers of cell behaviors. Conventional cell culture biomaterials, with static mechanical properties such as chemistry, topography, and stiffness, have offered a fundamental understanding of various vital biochemical and biophysical processes, such as cell adhesion, spreading, migration, growth, and differentiation. At present, novel biomaterials that can spatiotemporally impart biophysical cues to manipulate cell fate are emerging. The dynamic properties and adaptive traits of new materials endow them with the ability to adapt to cell requirements and enhance cell functions. In this review, an introductory overview of the key players essential to mechanobiology is provided. A biophysical perspective on the state-of-the-art manipulation techniques and novel materials in designing static and dynamic ECM-mimicking biomaterials is taken. In particular, different static and dynamic mechanical cues in regulating cellular mechanosensing and functions are compared. This review to benefit the development of engineering biomechanical systems regulating cell functions is expected.

Surface Plasmon Resonance (SPR) biosensor for detection of mycotoxins: A review.

Mycotoxin is one of the most important natural pollutants, which poses a global threat to food safety. However, the pollution of mold in food production is inevitable. The detection technology of mycotoxins in food production is an important means to prevent the damage of mycotoxins, so rapid detection and screening to avoid pollution diffusion is essential. The focus of this review is to update the literature on the detection of mycotoxins by surface plasmon resonance (SPR) technology, rather than just traditional chromatographic methods. As a relatively novel and simple analytical method, SPR has been proved to be fast, sensitive and label-free, and has been widely used in real-time qualitative and quantitative analysis of various pollutants. This paper aims to give a broad overview of the sensors for detection and analysis of several common mycotoxins.

A One-step strategy to target essential factors with auxin-inducible degron system in mouse embryonic stem cells.

The self-renewal and pluripotency of embryonic stem cells (ESCs) are conferred by networks including transcription factors and histone modifiers. The Auxin-inducible degron (AID) system can rapidly and reversibly degrade its target proteins and is becoming a powerful tool to explore novel function of key pluripotent and histone modifier genes in ESCs. However, the low biallelic tagging efficiency and a basal degradation level of the current AID systems deem it unsuitable to target key pluripotent genes with tightly controlled expression levels. Here, we develop a one-step strategy to successfully target and repress the endogenous pluripotent genes in mouse ESCs and replace their expression with AID fused transgenes. Therefore, this work provides an efficient way for employing the AID system to uncover novel function of essential pluripotent and chromatin modifier genes in ESCs.

A Versatile, Incubator-Compatible, Monolithic GaN Photonic Chipscope for Label-Free Monitoring of Live Cell Activities.

The ability to quantitatively monitor various cellular activities is critical for understanding their biological functions and the therapeutic response of cells to drugs. Unfortunately, existing approaches such as fluorescent staining and impedance-based methods are often hindered by their multiple time-consuming preparation steps, sophisticated labeling procedures, and complicated apparatus. The cost-effective, monolithic gallium nitride (GaN) photonic chip has been demonstrated as an ultrasensitive and ultracompact optical refractometer in a previous work, but it has never been applied to cell studies. Here, for the first time, the so-called GaN chipscope is proposed to quantitatively monitor the progression of different intracellular processes in a label-free manner. Specifically, the GaN-based monolithic chip enables not only a photoelectric readout of cellular/subcellular refractive index changes but also the direct imaging of cellular/subcellular ultrastructural features using a customized differential interference contrast (DIC) microscope. The miniaturized chipscope adopts an ultracompact design, which can be readily mounted with conventional cell culture dishes and placed inside standard cell incubators for real-time observation of cell activities. As a proof-of-concept demonstration, its applications are explored in 1) cell adhesion dynamics monitoring, 2) drug screening, and 3) cell differentiation studies, highlighting its potential in broad fundamental cell biology studies as well as in clinical applications.

"Raspberry" Hierarchical Topographic Features Regulate Human Mesenchymal Stem Cell Adhesion and Differentiation via Enhanced Mechanosensing.

An understanding of cellular mechanoresponses to well-defined synthetic topographic features is crucial for the fundamental research and biomedical applications of stem cells. Structured biointerfaces, in particular the ones with nanometer and/or micrometer surficial features, have drawn more attention in the past few decades. However, it is still difficult to integrate nanostructures and microstructures onto the synthesized biointerfaces to mimic the hierarchical architecture of the native extracellular matrix (ECM). Herein, a series of "raspberry"-like hierarchical surfaces with well-defined nanofeatures and tunable nano/microfeatures have been achieved via a catecholic polymer coating technique. Cellular responses to these hierarchical interfaces were systemically studied, indicating that the nanofeatures on the raspberry surfaces significantly enhanced the mechanosensing of human mesenchymal stem cells (hMSCs) to interfacial physical cues. Cell mechanotransduction was further investigated by analyzing focal adhesion assembling, cytoskeleton organization, cell nuclear mechanics, and transcriptional activity. The results suggest that nanosize surficial features could increase cellular mechanosensing to environment physical cues. The mechanotransduction and cell fate specification were greatly enhanced by the ECM mimicking nano/microhierarchical biointerfaces but the features should be in an optimized size.

Clonality, virulence genes, and antibiotic resistance of Staphylococcus aureus isolated from blood in Shandong, China.

BACKGROUND: Bloodstream infection (BSI) caused by Staphylococcus aureus (S. aureus) can be life-threatening and pose a great challenge to infection control and clinical treatment. However, little information exists regarding the characterization of S. aureus in BSI patients in Shandong, China. To identify the clonality, virulence genes, and antibiotic resistance of S. aureus in blood, a total of 101 nonrepetitive blood isolates were collected. The antibiotic resistance phenotypes were determined, and virulence genes were analyzed with polymerase chain reaction (PCR). Finally, the genetic relatedness was investigated with Staphylococcus chromosomal cassette mec (SCCmec) typing for methicillin-resistant S. aureus (MRSA) isolates, Staphylococcal protein A (spa), and multilocus sequence typing (MLST) for all of 101 isolates. RESULTS: Of the 101 S. aureus isolates, 24 MRSA isolates and 77 methicillin-susceptible S. aureus (MSSA) isolates were identified. Overall, MRSA isolates had higher resistance rates than MSSA isolates when exposed to any of the 15 antibiotics tested in this study except for trimethoprim/sulfamethoxazole. Among the 17 virulence genes tested in this study, hla, hld, and hlg could be detected in all isolates. MRSA isolates were more likely to carry seb and hlb genes, while MSSA isolates were more likely to carry seg and sei genes. Thirty-five sequence types (STs) and 49 spa types were identified, of which ST59-t437 and ST398-t571 were the most abundant. These two genotypes were also the most abundant ST-spa types in MRSA and MSSA isolates, but their abundances shifted over time, with ST398-t571 being the predominant genotype from 2016 to 2017, and ST59-t437 from 2018 to 2020. Besides, all the ST59-t437 isolates harbored hlgb gene, whereas most (88.9%) ST398-t571 did not. In addition, twenty-four MRSA isolates were subject to SCCmec typing. SCCmec IVa was the most prevalent SCCmec type, and all the ST59-t437 MRSA isolates were SCCmec IVa. We also observed 15 new STs, and some of them were MRSA. CONCLUSION: These findings provide additional observations and epidemiological data for blood S. aureus isolates, which can improve future infection-control measures and aid in potential clinical treatments in hospitals and other clinical settings.

Dietary supplementation with acidifiers improves the growth performance, meat quality and intestinal health of broiler chickens.

This experiment was conducted to study the effects of dietary supplementation with acidifiers on the growth performance, meat quality, and intestinal health of broiler chickens. A total of 648 male Arbor Acres broiler chickens at 1 d old were randomly divided into 6 groups, and each group consisted of 6 replicates with 18 broilers per replicate. The dietary treatments were as follows: negative control (NC, the basal diet), NC + antibiotic (enramycin, 8 mg/kg, positive control [PC]), NC + phosphoric acid (PA, 0.1, 0.2, and 0.3 g/kg), and NC + lactic acid (LA, 0.3 g/kg). The feeding trial lasted for 42 d. The results showed that the feed-to-gain ratio of the NC + acidifier groups was lower than that of the NC and PC groups from 1 to 42 d (P < 0.05). Compared with the values in the NC group, the pH of breast muscle was significantly higher in the NC + PA (0.2 g/kg) and LA (0.3 g/kg) groups (P < 0.05), and the cooking loss was lower in the breast muscle of the NC + PA (0.1 g/kg) and LA (0.3 g/kg) groups (P < 0.05). In addition, the shear force of the breast muscle and thigh muscle and the pH value in the crop, gizzard and duodenum of the antibiotic and acidifier groups were significantly decreased (P < 0.05). Moreover, the trypsin, chymotrypsin, and lipase activities of the duodenum in the NC + PA (0.2 and 0.3 g/kg) groups, as well as the villus height-to-crypt depth (VH:CD) ratio of the duodenum in the NC + PA (0.1 g/kg) group was significantly greater (P < 0.05) compared with those in the NC group. Meanwhile, the number of total aerobic bacteria, Escherichia coli and Salmonella in the cecum of the NC + PA (0.1 g/kg) and LA (0.3 g/kg) groups were decreased (P < 0.05). Collectively, diet supplementation with acidifiers could improve the growth performance, meat quality, and intestinal health of broilers, in which the effects of PA (0.1 g/kg and 0.2 g/kg) are better than the other supplementations.

Eggerthella lenta Bacteremia in a Middle-Aged Healthy Man with Acute Hepatic Abscess: Case Report and Literature Review, 1970-2020.

Eggerthella lenta (E. lenta) is a rare but significant human emerging pathogen. Infections caused by it are rare and little-known, both on clinical and therapeutical aspects, in spite of new emergence of bacteria isolation and identification techniques. In this article, we report a case involving a previously healthy 52-year-old man suffering from a newly diagnosed hepatic abscess who developed E. lenta bacteremia, which was treated successfully using empirical therapy with ertapenem and teicoplanin. To the best of our knowledge, this is the first documented report of E. lenta bacteremia related specifically to liver abscess. Cases related to this bacterial species are infrequent and sporadic; thus, we reviewed English literature on E. lenta infection in PubMed/MEDLINE in the last 50 years. A total of 31 sporadic cases were identified. The majority of patients were male (71%), had an average age of 54.3 years and presented predisposing conditions, such as digestive system trouble (45.2%), immunocompromised state (25.8%) or risk factors (22.6%). Two of the cases had more than one predisposing factors. Fever was common (93.5%). Average days to diagnosis of them were 6.8 days. MALDI-TOF MS is emerging as a fast and useful tool in the identification of it. Teicoplanin, vancomycin, amoxicillin-clavulanate, metronidazole, clindamycin, cefoxitin, chloramphenicol, and carbapenems appear to be the most used antibiotic treatment options. The purpose of this review is to increase awareness about the clinical infections caused by E. lenta.

Long-term effects of maize straw return and manure on the microbial community in cinnamon soil in Northern China using 16S rRNA sequencing.

Excessive use of chemical fertilizers in agricultural practices have demonstrated a significant impact on microbial diversity and community in soil by altering soil physical and chemical properties, thereby leading to a certain degree of soil salinization and nutritional imbalances. As an organic amendment, maize straw has been widely used to improve soil quality; however, its effect on the soil bacterial community remains limited in Calcarie-Fluvie Cambisols soil in semi-humid arid plateau of North China. In the present experiment, we investigated the effects of continuous straw utilization and fertilization on bacterial communities in Shouyang, Shanxi province, China. Soil samples were collected from 5 different straw utilization and fertilization modes in the following ways: straw mulching (SM), straw crushing (SC), cattle manure (CM), in which way straw is firstly used as silage and then organic fertilizer, control with no straw return (NSR), and control without fertilizers (CK), same amount of N+P fertilizer was applied to the regimes except CK. High-throughput sequencing approaches were applied to the V3-V4 regions of the 16S ribosomal RNA for analysis of the bacterial abundance and community structures. Different long-term straw returning regimes significantly altered the physicochemical properties and bacterial communities of soil, among which CM had the most significant effects on soil fertility and bacterial diversity. Proteobacteria, Actinobacteria, Chloroflexi, Acidobacteria, and Gemmatimonadetes were consistently dominant in all soil samples, and Redundancy analysis (RDA) showed significant association of total nitrogen (TN), total phosphorus (TP) and available potassium (AK) with alternation of the bacterial community. Cattle manure had the most beneficial effects on soil fertility and bacterial diversity among different straw utilization and fertilization modes.

Wilms' Tumor 1-Associated Protein Contributes to Chemo-Resistance to Cisplatin Through the Wnt/ß-Catenin Pathway in Endometrial Cancer.

BACKGROUND: Cisplatin remains the mainstay of endometrial cancer (EC) chemotherapy. Wilms' tumor 1-associated protein (WTAP), playing a critical role in transcriptional and post-transcriptional regulation, has been reported as an oncogene, and its expression is elevated in multiple types of human tumors. Recent evidence has shown that the increased expression of WTAP is also closely related to chemo-resistance. However, its specific role in the susceptibility of human EC cells to cisplatin remains largely unexplored. METHODS: WTAP over-expression and WTAP depletion cell lines as well as their corresponding controls were constructed by transfection with lentivirus. Western blotting analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to detect the expression of WTAP. Cell proliferation assay, colony formation assay, cell cycle assay, and apoptosis analysis were adopted to evaluate the effect of WTAP on the chemo-sensitivity of EC cells to cisplatin as well as its underlying mechanism. Immunofluorescence staining was used to assess the translocation of ß-catenin. Moreover, a subcutaneous xenograft tumor model was established to assess the effect of WTAP on tumor growth after cisplatin treatment. RESULTS: Depletion of WTAP in RL95-2 cells significantly enhanced the chemo-susceptibility of cells to cisplatin and increased the cell apoptosis, while WTAP over-expression in ARK-2 cells exhibited the opposite effects. Additionally, WTAP depletion significantly suppressed xenograft-tumor growth and enhanced sensitivity and apoptosis of tumor cells in vivo. Mechanistic analysis exhibited that WTAP over-expression facilitated the cytoplasm-to-nucleus translocation of ß-catenin and enhanced the GSK3ß phosphorylation at Ser9, while WTAP depletion revealed the opposite results, indicating that WTAP rendered chemo-resistance of EC cells to cisplatin by promoting the Wnt/ß-catenin pathway. CONCLUSIONS: WTAP might promote the chemo-resistance of EC cells to cisplatin through activating the Wnt/ß-catenin pathway. Collectively, our findings offered novel insights into EC treatment.

Self-Strengthening Adhesive Force Promotes Cell Mechanotransduction.

The extracellular matrix (ECM) undergoes dynamic remodeling and progressive stiffening during tissue regeneration and disease progression. However, most of the artificial ECMs and in vitro disease models are mechanically static. Here, a self-strengthening polymer coating mimicking the dynamic nature of native ECM is designed to study the cellular response to dynamic biophysical cues and promote cell mechanical sensitive response. Spiropyran (SP) is utilized as dynamic anchor group to regulate the strength of cell adhesive peptide ligands. Benefiting from spontaneous thermal merocyanine-to-spiropyran (MC-SP) isomerization, the resulting self-responsive coating displays dynamic self-strengthening of interfacial interactions. Comparing with the static and all of the previous dynamic artificial ECMs, cells on this self-responsive surface remodel the weakly bonded MC-based coatings to activate α5ß1 integrin and Rac signaling in the early adhesion stage. The subsequent MC-to-SP conversion strengthens the ligand-integrin interaction to further activate αvß3 integrin and RhoA/ROCK signaling in the latter stage. This sequential process enhances cellular mechanotransduction as well as the osteogenic differentiation of mesenchymal stem cells (MSCs). It is worth emphasizing that the self-strengthening occurs spontaneously in the absence of any stimulus, making it especially useful for implanted scaffolds in regenerative medicine.

Zinc transporter SLC39A7 relieves zinc deficiency to suppress alternative macrophage activation and impairment of phagocytosis.

Macrophages are key phagocytic cells and play an important role in eliminating external microorganisms and endogenous danger signals. Dysregulation in macrophage functions have been reported in patients with asthma. Zinc homeostasis is critical in maintaining macrophage functions. The solute carrier (SLC) protein SLC39A7, a Zn2+ importer, has recently been linked to asthma. However, the roles of SLC39A7 in macrophage phagocytosis are not well understood. Here we found that phagocytosis efficiency was significantly decreased in SLC39A7-knockdown THP-1 cells, however the phagocytosis capability could be reversed with zinc supplementation. SLC39A7 deficiency skewed macrophages towards alternative activation, as indicated by increased expression of M2 activation marker CD206 and decreased expression of M1 activation marker NOS2. Consistent to this result, SLC39A7-knockdown cells produced reduced amounts of proinflammatory cytokines TNF- and IL-6. Furthermore, the mRNA level of receptor Clec4e previously known to be involved in phagocytosis of BCG was significantly reduced in SLC39A7 knockdown cells. Importantly, all these defects due to SLC39A7 deficiency could be reversed by zinc supplementation. Thus, zinc transporter SLC39A7 provide support for phagocytosis and classical macrophage activation.

Ligand Diffusion Enables Force-Independent Cell Adhesion via Activating α5ß1 Integrin and Initiating Rac and RhoA Signaling.

Cells reside in a dynamic microenvironment in which adhesive ligand availability, density, and diffusivity are key factors regulating cellular behavior. Here, the cellular response to integrin-binding ligand dynamics by directly controlling ligand diffusivity via tunable ligand-surface interactions is investigated. Interestingly, cell spread on the surfaces with fast ligand diffusion is independent of myosin-based force generation. Fast ligand diffusion enhances α5ß1 but not αvß3 integrin activation and initiates Rac and RhoA but not ROCK signaling, resulting in lamellipodium-based fast cell spreading. Meanwhile, on surfaces with immobile ligands, αvß3 and α5ß1 integrins synergistically initiate intracellular-force-based canonical mechanotransduction pathways to enhance cell adhesion and osteogenic differentiation of stem cells. These results indicate the presence of heretofore-unrecognized pathways, distinct from canonical actomyosin-driven mechanisms, that are capable of promoting cell adhesion.

Surface Roughness Gradients Reveal Topography-Specific Mechanosensitive Responses in Human Mesenchymal Stem Cells.

The topographic features of an implant, which mechanically regulate cell behaviors and functions, are critical for the clinical success in tissue regeneration. How cells sense and respond to the topographical cues, e.g., interfacial roughness, is yet to be fully understood and even debatable. Here, the mechanotransduction and fate determination of human mesenchymal stem cells (MSCs) on surface roughness gradients are systematically studied. The broad range of topographical scales and high-throughput imaging is achieved based on a catecholic polyglycerol coating fabricated by a one-step-tilted dip-coating approach. It is revealed that the adhesion of MSCs is biphasically regulated by interfacial roughness. The cell mechanotransduction is investigated from focal adhesion to transcriptional activity, which explains that cellular response to interfacial roughness undergoes a direct force-dependent mechanism. Moreover, the optimized roughness for promoting cell fate specification is explored.

Surface Roughness and Substrate Stiffness Synergize To Drive Cellular Mechanoresponse.

Material surface topographic features have been shown to be crucial for tissue regeneration and surface treatment of implanted devices. Many biomaterials were investigated with respect to the response of cells on surface roughness. However, some conclusions even conflicted with each other due to the unclear interplay of surface topographic features and substrate elastic features as well as the lack of mechanistic studies. Herein, wide-scale surface roughness gradient hydrogels, integrating the surface roughness from nanoscale to microscale with controllable stiffness, were developed via soft lithography with precise surface morphology. Based on this promising platform, we systematically studied the mechanosensitive response of human mesenchymal stem cells (MSCs) to a broad range of roughnesses (200 nm to 1.2 µm for Rq) and different substrate stiffnesses. We observed that MSCs responded to surface roughness in a stiffness-dependent manner by reorganizing the surface hierarchical structure. Surprisingly, the cellular mechanoresponse and osteogenesis were obviously enhanced on very soft hydrogels (3.8 kPa) with high surface roughness, which was comparable to or even better than that on smooth stiff substrates. These findings extend our understanding of the interactions between cells and biomaterials, highlighting an effective noninvasive approach to regulate stem cell fate via synergetic physical cues.