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Recently, the existence of massless chiral (Weyl) fermions has been postulated in a class of semi-metals with a non-trivial energy dispersion. These materials are now commonly dubbed Weyl semi-metals (WSM). One predicted property of Weyl fermions is the chiral or Adler-Bell-Jackiw anomaly, a chirality imbalance in the presence of parallel magnetic and electric fields. In WSM, it is expected to induce a negative longitudinal magnetoresistance (MR). Here, we present experimental evidence that the observation of the chiral anomaly can be hindered by an effect called 'current jetting'. This effect also leads to a strong apparent negative longitudinal MR, but it is characterized by a highly non-uniform current distribution inside the sample. It appears in materials possessing a large field-induced anisotropy of the resistivity tensor, such as almost compensated high-mobility semimetals due to the orbital effect. In case of a non-homogeneous current injection, the potential distribution is strongly distorted in the sample. As a consequence, an experimentally measured potential difference is not proportional to the intrinsic resistance. Our results on the MR of the Weyl semimetal candidate materials NbP, NbAs, TaAs, and TaP exhibit distinct signatures of an inhomogeneous current distribution, such as a field-induced 'zero resistance' and a strong dependence of the 'measured resistance' on the position, shape, and type of the voltage and current contacts on the sample. A misalignment between the current and the magnetic-field directions can even induce a 'negative resistance'. Finite-element simulations of the potential distribution inside the sample, using typical resistance anisotropies, are in good agreement with the experimental findings. Our study demonstrates that great care must be taken before interpreting measurements of a negative longitudinal MR as evidence for the chiral anomaly in putative Weyl semimetals.

Hyaluronan (HA) is a critical element of the extracellular matrix (ECM). The regulated synthesis and degradation of HA modulates the ECM chemical and physical properties that, in turn, influence cellular behavior. HA triggers signaling pathways associated with the adhesion, proliferation, migration, and differentiation of cells, mediated by its interaction with specific cellular receptors or by tuning the mechanical properties of the ECM. This review summarizes the recent advances on strategies used to mimic the HA present in the ECM to study healthy or pathological cellular behavior. This includes the development of HA-based 2D and 3D in vitro tissue models for the seeding and encapsulation of cells, respectively, and HA particles as carriers for the targeted delivery of therapeutic agents. The extracellular matrix is composed of hyaluronan of different molecular weights that play different roles in cellular proliferation, migration, and differentiation.The dysregulated accumulation of hyaluronan alters the mechanical and biochemical properties of the extracellular matrix and it is associated with several pathological states.Biomaterials can be engineered using the native hyaluronan backbone or chemically modified to target cells via specific cellular receptors, such as CD44.2D surfaces with controlled topography and 3D hydrogels with tuned mechanical properties and hyaluronan composition can be designed to mimic the bioactivity of this glycosaminoglycan in the ECM.

Hydrogels for nucleus pulposus (NP) regeneration should be able to comprise a nonangiogenic or even antiangiogenic feature. Gellan gum (GG)–based hydrogels have been reported to possess adequate properties for being used as NP substitutes in acellular and cellular strategies, due to its ability to support cell encapsulation, adequate mechanical properties, and noncytotoxicity. In this study, the angiogenic response of GG-based hydrogels was investigated by performing the chorioallantoic membrane assay. The convergence of macroscopic blood vessels toward the GG, ionic-crosslinked methacrylated GG (iGG-MA), and photo-crosslinked methacrylated GG (phGG-MA) hydrogel discs was quantified. Gelatin sponge (GSp) and filter paper (FP) alone and with vascular endothelial growth factor were used as controls of angiogenesis. The images obtained were digitally processed and analyzed by three independent observers. The macroscopic blood vessel quantification demonstrated that the GG-based hydrogels are not angiogenic as compared with FP controls. No statistical differences between the GG-based hydrogels tested in respect to its angiogenic ability were observed. Hematoxylin and eosin staining and SNA-lectin immunohistochemistry assay indicated that the iGG-MA and phGG-MA hydrogels do not allow the ingrowth of chick endothelial cells, following 4 days of implantation. On the contrary, GG, GSp, and FP controls allowed cell infiltration. The histological data also indicated that the GG-based hydrogels do not elicit any acute inflammatory response. The results showed that the GG, iGG-MA, and phGG-MA hydrogels present different permeability to cells but functioned as a physical barrier for vascular invasion. These hydrogels present promising and tunable properties for being used as NP substitutes in the treatment of degenerative intervertebral disc.

The past 20 years have witnessed ever- growing evidence that the mechanical properties of biological tissues, from nanoscale to macroscale dimensions, are fundamental for cellular behaviour and consequent tissue functionality. This knowledge, combined with previously known biochemical cues, has greatly advanced the field of biomaterial development, tissue engineering and regenerative medicine. It is now established that approaches to engineer biological tissues must integrate and approximate the mechanics, both static and dynamic, of native tissues. Nevertheless, the literature on the mechanical properties of biological tissues differs greatly in methodology, and the available data are widely dispersed. This Review gathers together the most important data on the stiffness of living tissues and discusses the intricacies of tissue stiffness from a materials perspective, highlighting the main challenges associated with engineering lifelike tissues and proposing a unified view of this as yet unreported topic. Emerging advances that might pave the way for the next decadeâ s take on bioengineered tissue stiffness are also presented, and differences and similarities between tissues in health and disease are discussed, along with various techniques for characterizing tissue stiffness at various dimensions from individual cells to organs.

Protein-based hydrogels with distinct conformations which enable encapsulation or differentiation of cells are of great interest in 3D cancer research models. Conformational changes may cause macroscopic shifts in the hydrogels, allowing for its use as biosensors and drug carriers. In depth knowledge on how 3D conformational changes in proteins may affect cell fate and tumor formation is required. Thus, this study reports an enzymatically crosslinked silk fibroin (SF) hydrogel system that can undergo intrinsic conformation changes from random coil to β-sheet conformation. In random coil status, the SF hydrogels are transparent, elastic, and present ionic strength and pH stimuli-responses. The random coil hydrogels become β-sheet conformation after 10 days in vitro incubation and 14 days in vivo subcutaneous implantation in rat. When encapsulated with ATDC-5 cells, the random coil SF hydrogel promotes cell survival up to 7 days, whereas the subsequent β-sheet transition induces cell apoptosis in vitro. HeLa cells are further incorporated in SF hydrogels and the constructs are investigated in vitro and in an in vivo chick chorioallantoic membrane model for tumor formation. In vivo, Angiogenesis and tumor formation are suppressed in SF hydrogels. Therefore, these hydrogels provide new insights for cancer research and uses of biomaterials.

L.W. and L.D. contributed equally to this work. This study was supported by the National Natural Science Foundation of China (82072060 and 22008201), the Fundamental Research Funds for the Central Universities (SWU-XDPY22006), the Venture and Innovation Support Program for Chongqing Overseas Returnees (2205012980212766), the Distinguished Young Scholars of Chongqing (2022NSCQ-JQX5279), and the Natural Science Foundation Project of Chongqing (cstc2020jcyj-msxmX0292). All animal protocols in this study were approved by the Institutional Animal Care and Use Committee of Southwest University (No. IACUC-20211120-05).

JO thanks the FCT for the funds provided under the program Investigador FCT 2015 (IF/01285/2015). The authors are also thankful to the FCT funded project NanoOptoNerv (ref. PTDC/NAN-MAT/29936/2017). And to the project Nano-accelerated nerve regeneration and optogenetic empowering of neuromuscular functionality (ref. PTDC/NAN-MAT/29936/2017).

In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissuesâ extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies.

Fluid milk and its derivatives are important dietary ingredients that contribute to daily nutrient intake of the modern Homo sapiens. To produce milk that is healthier for human consumption, the present study evaluated the effect of adding soybean oil and linseed oil in the diet of lactating cows. The fatty acid profile of milk, milk composition, and the blood parameters of cows were evaluated. Eighteen Holstein cows were distributed in a replicated Latin square design and distributed according to the following treatments: 1) Control (CC): traditional dairy cow diet, without addition of oil; 2) Soybean oil (SO): 2.5% addition of soybean oil to the traditional diet, as a source of omega-6; 3) Linseed oil (LO): 2.5% addition of linseed oil in the diet as a source of omega-3. Milk production was not affected, but oil supplementation decreased feed intake by 1.93 kg/cow/day. The milk fat percentage was significantly lower when cows were supplemented with vegetable oil (3.37, 2.75 and 2.89% for CC, SO and LO, respectively). However, both soybean and linseed oils decreased the concentration of saturated fatty acids (66.89, 56.52 and 56.60 g/100g for CC, SO and LO respectively), increased the amount of unsaturated fatty acids in milk (33.05, 43.39, and 43.35 g/100g for CC, SO and LO respectively) and decreased the ratio between saturated/unsaturated fatty acids (2.12, 1.34, and 1.36 for CC, SO and LO respectively). Furthermore, SO and LO increased significantly the concentration of monounsaturated fatty acids (29.58, 39.55 and 39.47 g/100g for CC, SO and LO respectively), though it did not significantly alter the level of polyunsaturated fatty acids in milk fat (3.57, 3.93 and 3.98 g/100g for CC, SO and LO respectively). Supplementation with LO enhanced the concentration of omega-3 fatty acids on milk (0.32, 0.36, and 1.02 for CC, SO and LO respectively). Blood variables aspartate aminotransferase, gamma glutamyl transferase, urea, albumin, creatinine and total proteins were not altered. On the other hand, total cholesterol, HDL and LDL were greater in the group supplemented with vegetable oils. Supplementation with vegetable oils reduced the dry matter intake of cows, the fat content of milk, and improved saturated/unsaturated fatty acid ratio of milk fat. Compared to the SO treatment, animals fed LO produced milk with greater content of omega-3, and a more desirable omega-6/omega-3 ratio on a human nutrition perspective. Thus, the inclusion of SO and LO in the diet of lactating dairy cows makes the milk fatty acid profile nutritionally healthier for the human consumption.

In tumors, somatic mutations of the PTEN suppressor gene are associated with advanced disease, chemotherapy resistance, and poor survival. PTEN loss of function may occur by inactivating mutation, by deletion, either affecting one copy (hemizygous loss) leading to reduced gene expression or loss of both copies (homozygous) with expression absent. Various murine models have shown that minor reductions in PTEN protein levels strongly influence tumorigenesis. Most PTEN biomarker assays dichotomize PTEN (i.e. presence vs. absence) ignoring the role of one copy loss. We performed a PTEN copy number analysis of 9793 TCGA cases from 30 different tumor types. There were 419 (4.28%) homozygous and 2484 (25.37%) hemizygous PTEN losses. Hemizygous deletions led to reduced PTEN gene expression, accompanied by increased levels of instability and aneuploidy across tumor genomes. Outcome analysis of the pan-cancer cohort showed that losing one copy of PTEN reduced survival to comparable levels as complete loss, and was associated with transcriptomic changes controlling immune response and the tumor microenvironment. Immune cell abundances were significantly altered for PTEN loss, with changes in head and neck, cervix, stomach, prostate, brain, and colon more evident in hemizygous loss tumors. These data suggest that reduced expression of PTEN in tumors with hemizygous loss leads to tumor progression and influences anticancer immune response pathways.